PHARMACEUTICAL COMPOSITIONS CONTAINING COMPOUNDS WHICH INCREASE OR DECREASE TMTNF LEVELS

摘要

Described are pharmaceutical compositions comprising a compound which is capable of effecting an increased endothelial level of tmTNF, preferably this increase of the endothelial level of tmTNF is restricted to tumors. Increase of endothelial level of tmTNF results in an increase of VEGF-induced hyperpermeability leading to sensitization of tumors for the application of sTNF, thus allowing the treatment of tumors, which can so far only be treated with extremely high doses of sTNF or which are resistant to such a treatment. In addition, pharmaceutical compositions are described additionally containing a cytostatic drug, since by increasing endothelial hyperpermeability, not only a drastic improvement of the delivery of sTNF to the tumor can be achieved, but in addition this also allows to more efficiently deliver cytostatic drugs to the tumorKits for the diagnosis of tumors showing a reduced level of endothelial tmTNF are also described. Finally, the present invention relates to pharmaceutical compositions comprising a compound which is capable of effecting a decreased endothelial level of tmTNF or SAPK-2/p38 MAP. Such compositions are useful for the treatment of VEGF-mediated increased vascular permeability, e.g. as a side effect of therapeutic angiogenesis or which leads to edema formation in ischemic/hypoxic conditions.