title: Human Neural Stem Cells Overexpressing a Carboxylesterase Inhibit Bladder Tumor Growth.
abstract: Bladder cancer is a significant clinical and economic problem. Despite intravesical chemotherapy and immunotherapy, up to 80% of patients with non-muscle-invasive bladder cancer develop recurrent tumors, of which 20% to 30% evolve into more aggressive, potentially lethal tumors. Recently, bladder cancer cells are considered to be mediators of resistance to current therapies and therefore represent strong candidates as biologic targets. No effective chemotherapy has yet been developed for advanced bladder cancer. It is desirable that a drug can be delivered directly and specifically to bladder cancer cells. Stem cells have selective migration ability toward cancer cells, and therapeutic genes can be easily transduced into stem cells. In suicide gene therapy for cancer, stem cells carry a gene encoding a carboxylesterase (CE) enzyme that transforms an inert CPT-11 prodrug into a toxic SN-38 product, a topoisomerase 1 inhibitor. In immunodeficient mice, systemically transplanted HB1.F3.CE stem cells migrated toward the tumor implanted by the TCCSUP bladder cancer cell line, and, in combination with CPT-11, the volume of tumors was significantly reduced. These findings may contribute to the development of a new selective chemotherapeutic strategy against bladder cancer. Mol Cancer Ther; 15(6); 1201-7. ©2016 AACR.
authors.affiliation: Biomedical Research Institute, Chung-Ang University Hospital, Seoul, Republic of Korea.
authors.forename: Sung S
authors.initials: SS
authors.lastname: Choi
authors.affiliation: Department of Urology, Chung-Ang University College of Medicine, Seoul, Republic of Korea.
authors.forename: Byung Hoon
authors.initials: BH
authors.lastname: Chi
authors.affiliation: Department of Urology, Chung-Ang University College of Medicine, Seoul, Republic of Korea.
authors.forename: In Ho
authors.initials: IH
authors.lastname: Chang
authors.affiliation: Department of Urology, Chung-Ang University College of Medicine, Seoul, Republic of Korea.
authors.forename: Kyung Do
authors.initials: KD
authors.lastname: Kim
authors.affiliation: National Primate Research Center, Korea Research Institute of Bioscience and Biotechnology, Ochang, Chungbuk, Republic of Korea.
authors.forename: Sang-Rae
authors.initials: SR
authors.lastname: Lee
authors.affiliation: Division of Neurology, Department of Medicine, UBC Hospital, University of British Columbia, Vancouver, British Columbia, Canada. leehj71@gmail.com 1428rol@gmail.com.
authors.forename: Seung U
authors.initials: SU
authors.lastname: Kim
authors.affiliation: Biomedical Research Institute, Chung-Ang University Hospital, Seoul, Republic of Korea. leehj71@gmail.com 1428rol@gmail.com.
authors.forename: Hong J
authors.initials: HJ
authors.lastname: Lee
mesh_terms: D000818:Animals; D002166:Camptothecin / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000494:pharmacology; D043182:Carboxylesterase / Q000378:metabolism*; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D006801:Humans; D000077146:Irinotecan; D051379:Mice; D009368:Neoplasm Transplantation; D058953:Neural Stem Cells / Q000201:enzymology / Q000637:transplantation*; D011355:Prodrugs / Q000008:administration & dosage* / Q000494:pharmacology; D001749:Urinary Bladder Neoplasms / Q000201:enzymology / Q000628:therapy*
chemical_list: D011355:Prodrugs; D000077146:Irinotecan; D043182:Carboxylesterase; D002166:Camptothecin