title: Combined modality therapy of gemcitabine and irradiation on human glioma spheroids derived from cell lines and biopsy tissue.
abstract: Multicellular tumor spheroids have been used to examine aspects of combined modality treatment since they often recreate the in vivo tumor environment much more closely than other models. The radioenhancement by gemcitabine (dFdC) on human glioma spheroids derived from cell lines (CLS) and biopsy tissue, grown as organotypic multicellular spheroids (OMS), was studied. CLS of GaMg and U87 and OMS of four glioblastoma patients were used. Radiochemosensitvity was determined using migration and proliferation assays on CLS. In OMS, histology and immunohistochemical studies of MIB-1, p53, and p21 expression were examined 24 and 48 h following treatment. Cell death (ethidium homodimer) was studied using a fluorescence cell viability assay. In CLS, combination treatment led to migration inhibition in GaMg and U87 of 85% and 62% (dFdC 46% and 52%, RT 21% and 43%) and proliferation inhibition of 83% and 85%, respectively. Following dFdC + RT in OMS (% of cases), apoptosis and p21 expression increased (50%), p53 expression increased (75%) and cell proliferation decreased (75%). Only minor morphological damage was observed. Confocal laser scanning microscopy identified an increased dead cell core after dFdC + RT (50%). In conclusion, dFdC can lead to an additively radioenhancement in CLS and individual OMS.
authors.affiliation: Department of Radiation Oncology, University of Luebeck, Germany. fehlauer@uke.uni-hamburg.de
authors.forename: Fabian
authors.initials: F
authors.lastname: Fehlauer
authors.forename: Martina
authors.initials: M
authors.lastname: Muench
authors.forename: Ernst J
authors.initials: EJ
authors.lastname: Smid
authors.forename: Ben
authors.initials: B
authors.lastname: Slotman
authors.forename: Eckhard
authors.initials: E
authors.lastname: Richter
authors.forename: Paul
authors.initials: P
authors.lastname: Van der Valk
authors.forename: Peter
authors.initials: P
authors.lastname: Sminia
mesh_terms: D000964:Antimetabolites, Antineoplastic / Q000494:pharmacology / Q000627:therapeutic use; D017209:Apoptosis; D001932:Brain Neoplasms / Q000188:drug therapy / Q000473:pathology / Q000532:radiotherapy*; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D003131:Combined Modality Therapy; D003841:Deoxycytidine / Q000031:analogs & derivatives* / Q000494:pharmacology / Q000627:therapeutic use; D005910:Glioma / Q000188:drug therapy / Q000473:pathology / Q000532:radiotherapy*; D006801:Humans; D007150:Immunohistochemistry; D019394:Ki-67 Antigen / Q000032:analysis; D018613:Microscopy, Confocal; D016283:Proto-Oncogene Proteins p21(ras) / Q000032:analysis; D011838:Radiation-Sensitizing Agents / Q000494:pharmacology; D018874:Spheroids, Cellular; D016159:Tumor Suppressor Protein p53 / Q000032:analysis; D000093542:Gemcitabine
chemical_list: D000964:Antimetabolites, Antineoplastic; D019394:Ki-67 Antigen; D011838:Radiation-Sensitizing Agents; D016159:Tumor Suppressor Protein p53; D003841:Deoxycytidine; D016283:Proto-Oncogene Proteins p21(ras); D000093542:Gemcitabine