0000000000807315
AUTHOR
Jan-georg Hengstler
cAMP-dependent phosphorylation of CYP2B1 as a functional switch for cyclophosphamide activation and its hormonal controlin vitro andin vivo
An important feature of cytochrome P450 (CYP) 2B1 is its high ability to convert the prodrug cyclophosphamide (CPA) to therapeutically cytotoxic metabolites, resulting in interstrand DNA-cross-linking and cell death. We have examined whether and how the phosphorylation of CYP2B1 influences CPA metabolic activation in vitro and in vivo. We found first that only part of the total CYP2B1 pool undergoes phosphorylation. This part is fully inactivated. Second, phosphorylation of CYP2B1 in intact hepatocytes reduced by up to 75% toxification of CPA to mutagenic metabolites (totally dependent on the same preferentially CYP2B-catalyzed 4-hydroxylation of CPA as is the generation of highly cytotoxic…
Staging small cell lung cancer: Veterans Administration Lung Study Group versus International Association for the Study of Lung Cancer--what limits limited disease?
Small cell lung cancer (SCLC) is usually classified into a two-stage system, limited (LD) and extensive disease (ED). However, the criteria for these two categories remain controversial. The widely used Veterans Administration Lung Study Group (VALG) definition of LD includes patients with primary tumor and nodal involvement limited to one hemithorax. In contrast, the International Association for the Study of Lung Cancer (IASLC) recommends that LD should additionally include all patients without distant metastasis. As a consequence, since treatment modalities for LD and ED could be different, individual clinical outcome of SCLC patients may be influenced by the staging system chosen. Among…