655. Development of a Human Carboxylesterase That Can Efficiently Metabolize CPT-11
نویسندگان
چکیده
منابع مشابه
Effect of Cellular Location of Human Carboxylesterase 2 on CPT-11 Hydrolysis and Anticancer Activity
CPT-11 is an anticancer prodrug that is clinically used for the treatment of metastatic colorectal cancer. Hydrolysis of CPT-11 by human carboxylesterase 2 (CE2) generates SN-38, a topoisomerase I inhibitor that is the active anti-tumor agent. Expression of CE2 in cancer cells is under investigation for the tumor-localized activation of CPT-11. CE2 is normally expressed in the endoplasmic retic...
متن کاملCharacterization of CPT-11 hydrolysis by human liver carboxylesterase isoforms hCE-1 and hCE-2.
7-Ethyl-10-[4-(1-piperidino)-1-piperidino] carbonyloxy-camptothecin (irinotecan; CPT-11) is a prodrug activated by carboxylesterase enzymes. We characterized the hydrolysis of CPT-11 by two recently identified human carboxylesterase (hCE) enzymes, hCE-1 and hCE-2. Km and Vmax for hCE-1 and hCE-2 are 43 microM and 0.53 nmol/min/mg protein and 3.4 microM and 2.5 nmol/min/mg protein, respectively....
متن کاملSensitization of human tumor cells to CPT-11 via adenoviral-mediated delivery of a rabbit liver carboxylesterase.
Irinotecan, 7-ethyl-10-[4-(1-piperidino)-1-piperidino]carbonyloxycamptothecin (CPT-11) is activated by carboxylesterases (CE) to yield the potent topoisomerase I inhibitor, SN-38. We have demonstrated previously that a rabbit liver CE is approximately 100-1000-fold more efficient at drug activation than a highly homologous human CE. In an attempt to use rabbit CE expression in combination with ...
متن کاملIn vivo human carboxylesterase cDNA gene transfer to activate the prodrug CPT-11 for local treatment of solid tumors.
To evaluate the concept that in vivo transfer of the human carboxylesterase gene will confer sensitivity of a solid tumor to the prodrug CPT-11 (irinotecan), we constructed an adenovirus vector (AdCMV.CE) carrying the human carboxylesterase gene driven by the cytomegalovirus (CMV) promoter, infected A549 human lung adenocarcinoma cells in vitro and in vivo, and evaluated cell growth over time. ...
متن کاملIrinotecan (CPT-11) metabolites in human bile and urine.
A female patient was treated with irinotecan (CPT-11) for liver metastatic colon carcinoma. She had a percutaneous biliary catheter because of extrahepatic biliary obstruction. The patient was treated with CPT-11 for three courses at doses of 350 mg/m2 for the first course and 300 mg/m2 for the remaining courses, given as a 30-min i. v. infusion. Metabolism studies in bile and urine were perfor...
متن کاملذخیره در منابع من
با ذخیره ی این منبع در منابع من، دسترسی به آن را برای استفاده های بعدی آسان تر کنید
ژورنال
عنوان ژورنال: Molecular Therapy
سال: 2006
ISSN: 1525-0016
DOI: 10.1016/j.ymthe.2006.08.731