title: In vitro antitumor activity of rebeccamycin analog (NSC# 655649) against pediatric solid tumors.
abstract: OBJECTIVE
  This study determined the in vitro antitumor activity of a rebeccamycin analog (NSC# 655649) using tetrazolium/formazan (MTT) and clonogenic assays against established pediatric cell lines and solid tumor specimens obtained from children.
  
  
  METHODS
  Tumor cells from 14 established cell lines and 20 patient specimens were exposed in vitro for 1 hour to NSC# 655649 at concentrations ranging from 0.015 to 15.0 microM. The cytotoxicity (IC50) of this agent against established cell lines was determined using both the MTT (cytotoxic) and clonogenic/soft agar cloning (cytostatic) assays. Tumor specimens from children undergoing biopsy or surgical resection were also evaluated in vitro against NSC# 655649 using the clonogenic assay. For studies using patient specimens, antitumor activity was measured by comparing the number of tumor colonies from NSC# 655649-treated cells with those from solvent-treated controls.
  
  
  RESULTS
  These studies showed that the mean IC50S using the MTT and clonogenic assays using established solid tumor cell lines were 0.94 and 0.51 microM, respectively. In general, for cell lines tested using both types of assays, the clonogenic assay resulted in a smaller IC50. The overall in vitro responses (< or = 50% survival compared to controls) using patient tumor specimens and the clonogenic assay were 35% (1.5 microM), 60% (7.5 microM), and 80% (15.0 microM). Of the 9 patients with neuroblastoma, responses to NSC# 655649 were seen in 33% (1.5 microM), 58% (7.5 microM), and 92% (15.0 microM) of the specimens. Prior chemotherapy did not appear to adversely affect in vitro responses.
  
  
  CONCLUSIONS
  NSC# 655649 appears to have broad antitumor activity in vitro against pediatric malignancies at drug concentrations achieved during adult phase I clinical trials. These studies support the further development of NSC# 655649 for solid tumors in children.
authors.affiliation: Department of Pediatrics, University of Texas Health Science Center, San Antonio, Texas 78284-7810, USA.
authors.forename: S
authors.initials: S
authors.lastname: Weitman
authors.forename: R
authors.initials: R
authors.lastname: Moore
authors.forename: H
authors.initials: H
authors.lastname: Barrera
authors.forename: N K
authors.initials: NK
authors.lastname: Cheung
authors.forename: E
authors.initials: E
authors.lastname: Izbicka
authors.forename: D D
authors.initials: DD
authors.lastname: Von Hoff
mesh_terms: D000617:Aminoglycosides; D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D000970:Antineoplastic Agents / Q000494:pharmacology*; D002227:Carbazoles; D002648:Child; D004354:Drug Screening Assays, Antitumor; D005960:Glucosides; D006801:Humans; D008527:Medulloblastoma / Q000188:drug therapy; D009369:Neoplasms / Q000188:drug therapy*; D009447:Neuroblastoma / Q000188:drug therapy; D012208:Rhabdomyosarcoma / Q000188:drug therapy; D012512:Sarcoma, Ewing / Q000188:drug therapy; D013778:Tetrazolium Salts; D013844:Thiazoles; D014407:Tumor Cells, Cultured / Q000187:drug effects
chemical_list: D000617:Aminoglycosides; D000900:Anti-Bacterial Agents; D000970:Antineoplastic Agents; D002227:Carbazoles; D005960:Glucosides; D013778:Tetrazolium Salts; D013844:Thiazoles; C093269:becatecarin; C022616:thiazolyl blue