Purpose: To improve the efficacy and reduce the gastrointestinal toxicity of the cancer prodrug, CPT-11, we have developed immunoconjugates of its active form, SN-38, and an anti-CEACAM5 antibody for targeted chemotherapy. Experimental Design: SN-38 conjugates of the anti-CEACAM5 monoclonal antibody, labetuzumab (hMN-14), varying in the nature of the cross-linker attachment at the drug's 20-hyd...

The anticancer prodrug, irinotecan, is converted to its active form 7-ethyl-10-hydroxycamptothecin (SN-38) by carboxylesterases, and SN-38 is inactivated by UDP-glucuronosyltransferase (UGT)1A1-mediated glucuronidation. UGT1A9 also mediates this reaction. In a recent study, it was reported that the UGT1A9 IVS1 399 (I399)C>T polymorphism is associated with increased SN-38 glucuronidation both in...

Non–small cell lung cancers (NSCLC) are associated with very dismal prognoses, and adjuvant chemotherapy, including irinotecan, taxanes, platin, and Vinca alkaloid derivatives, offers patients only slight clinical benefits. Part of the chemoresistance of NSCLCs results from the constitutive or anticancer drug-induced activation of the nuclear factor-KB (NF-KB) signaling pathways. The present st...

O-Methylguanine-DNA methyltransferase (MGMT) is a DNA repair protein that removes alkyl-adducts from the O-guanine in DNA and is a crucial defense against O-alkylating agentinduced cytotoxicity. We demonstrated here that two camptothecin (CPT)-resistant cell lines (CPT30 and KB100) were more sensitive to N,N -bis(2-chloroethyl)-N-nitrosurea (BCNU) than their parental cells. Enhanced sensitivity...