title: Effects of irradiation and cisplatin on human glioma spheroids: inhibition of cell proliferation and cell migration.
abstract: OBJECTIVE
  Investigation of cell migration and proliferation of human glioma cell line spheroids (CLS) and evaluation of morphology, apoptosis, and immunohistochemical expression of MIB-1, p53, and p21 of organotypic muticellular spheroids (OMS) following cisplatin (CDDP) and irradiation (RT).
  
  
  METHODS
  Spheroids of the GaMg glioma cell line and OMS prepared from biopsy tissue of six glioblastoma patients were used. Radiochemosensitvity (5 microg/ml CDDP followed by RT) 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.
  
  
  RESULTS
  Combination treatment led to a migration inhibition of 38% (CDDP 13%; RT 27%) and specific growth delay of 2.6 (CDDP 1.3; RT 2.1) in CLS. Cell cycle analysis after combination treatment showed an accumulation of cells in the G2/M phase. In OMS, apoptosis increased, cell proliferation decreased, and p53/p21 expression increased more pronounced following CDDP+RT. No morphological damage was observed.
  
  
  CONCLUSIONS
  CDDP can lead to enhancement of the RT effect in spheroids of both human glioma cell line spheroids and biopsy spheroids from glioblastoma specimens. The exerted effect is additive rather than synergistic.
authors.affiliation: Department of Radiation Oncology, Universitätsklinikum Eppendorf, University of Hamburg, Martinistr. 52, 20254, Hamburg, 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: Dirk
authors.initials: D
authors.lastname: Rades
authors.forename: Lukas J A
authors.initials: LJ
authors.lastname: Stalpers
authors.forename: Sieger
authors.initials: S
authors.lastname: Leenstra
authors.forename: Paul
authors.initials: P
authors.lastname: van  der Valk
authors.forename: Ben
authors.initials: B
authors.lastname: Slotman
authors.forename: Ernst J
authors.initials: EJ
authors.lastname: Smid
authors.forename: Peter
authors.initials: P
authors.lastname: Sminia
mesh_terms: D000970:Antineoplastic Agents / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects / Q000528:radiation effects; D014408:Biomarkers, Tumor / Q000378:metabolism*; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000187:drug effects / Q000528:radiation effects; D049109:Cell Proliferation / Q000187:drug effects / Q000528:radiation effects; D017024:Chemotherapy, Adjuvant; D002945:Cisplatin / Q000494:pharmacology*; D050759:Cyclin-Dependent Kinase Inhibitor p21 / Q000378:metabolism; D005434:Flow Cytometry; D015972:Gene Expression Regulation, Neoplastic; D005910:Glioma / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology / Q000532:radiotherapy*; D006801:Humans; D007150:Immunohistochemistry; D019394:Ki-67 Antigen / Q000378:metabolism; D018714:Radiotherapy, Adjuvant; D018874:Spheroids, Cellular; D013997:Time Factors; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism
chemical_list: D000970:Antineoplastic Agents; D014408:Biomarkers, Tumor; C493956:CDKN1A protein, human; D050759:Cyclin-Dependent Kinase Inhibitor p21; D019394:Ki-67 Antigen; D016159:Tumor Suppressor Protein p53; D002945:Cisplatin