title: The pediatric preclinical testing program: description of models and early testing results.
abstract: BACKGROUND
  The Pediatric Preclinical Testing Program (PPTP) is an initiative supported by the National Cancer Institute (NCI) to identify novel therapeutic agents that may have significant activity against childhood cancers. The PPTP has established panels of childhood cancer xenografts and cell lines to be used for in vivo and in vitro testing. These include panels for Wilms tumor, sarcomas (rhabdomyosarcoma, Ewing sarcoma, and osteosarcoma), neuroblastoma, brain tumors (glioblastoma, ependymoma, and medulloblastoma), rhabdoid tumors (CNS and renal), and acute lymphoblastic leukemia (ALL). Here, we describe the characteristics of the in vivo tumor panels and report results for the in vivo evaluation of two standard agents, vincristine and cyclophosphamide.
  
  
  METHODS
  Solid tumors were grown subcutaneously in immune-deficient mice and tumor dimensions were measured weekly. ALL xenografts were inoculated intravenously and human CD45-positive cells were enumerated weekly.
  
  
  RESULTS
  Vincristine-induced objective responses in 6 of 24 (25%) and cyclophosphamide-induced objective responses in 18 of 28 (64%) solid tumor models. Comparable assessments of high levels of activity for these two agents were obtained using a tumor growth delay (TGD) measure. Both agents induced regressions in each of the ALL models evaluated.
  
  
  CONCLUSIONS
  We have established 51 solid tumor and 10 ALL in vivo models. The models identify vincristine and cyclophosphamide as having broad-spectrum activity. The PPTP tumor panels appear to generally recapitulate the activity of these agents against specific childhood cancers and to have the potential for identifying novel agents having significant clinical activity.
authors.affiliation: Department of Molecular Pharmacology, St. Jude Children's Research Hospital, Memphis, Tennessee 38105, USA. peter.houghton@stjude.org
authors.forename: Peter J
authors.initials: PJ
authors.lastname: Houghton
authors.forename: Christopher L
authors.initials: CL
authors.lastname: Morton
authors.forename: Chandra
authors.initials: C
authors.lastname: Tucker
authors.forename: Debbie
authors.initials: D
authors.lastname: Payne
authors.forename: Edward
authors.initials: E
authors.lastname: Favours
authors.forename: Claire
authors.initials: C
authors.lastname: Cole
authors.forename: Richard
authors.initials: R
authors.lastname: Gorlick
authors.forename: E Anders
authors.initials: EA
authors.lastname: Kolb
authors.forename: Wendong
authors.initials: W
authors.lastname: Zhang
authors.forename: Richard
authors.initials: R
authors.lastname: Lock
authors.forename: Hernan
authors.initials: H
authors.lastname: Carol
authors.forename: Mimi
authors.initials: M
authors.lastname: Tajbakhsh
authors.forename: C Patrick
authors.initials: CP
authors.lastname: Reynolds
authors.forename: John M
authors.initials: JM
authors.lastname: Maris
authors.forename: Joshua
authors.initials: J
authors.lastname: Courtright
authors.forename: Stephen T
authors.initials: ST
authors.lastname: Keir
authors.forename: Henry S
authors.initials: HS
authors.lastname: Friedman
authors.forename: Charles
authors.initials: C
authors.lastname: Stopford
authors.forename: Joseph
authors.initials: J
authors.lastname: Zeidner
authors.forename: Jianrong
authors.initials: J
authors.lastname: Wu
authors.forename: Tiebin
authors.initials: T
authors.lastname: Liu
authors.forename: Catherine A
authors.initials: CA
authors.lastname: Billups
authors.forename: Javed
authors.initials: J
authors.lastname: Khan
authors.forename: Sherry
authors.initials: S
authors.lastname: Ansher
authors.forename: Jian
authors.initials: J
authors.lastname: Zhang
authors.forename: Malcolm A
authors.initials: MA
authors.lastname: Smith
mesh_terms: D000818:Animals; D049109:Cell Proliferation / Q000187:drug effects; D003520:Cyclophosphamide / Q000008:administration & dosage* / Q000494:pharmacology; D004195:Disease Models, Animal; D018572:Disease-Free Survival; D004334:Drug Administration Schedule; D005260:Female; D006801:Humans; D007274:Injections, Intraperitoneal; D051379:Mice; D008807:Mice, Inbred BALB C; D016688:Mice, Inbred NOD; D008819:Mice, Nude; D016513:Mice, SCID; D009369:Neoplasms / Q000188:drug therapy*; D016896:Treatment Outcome; D014750:Vincristine / Q000008:administration & dosage* / Q000494:pharmacology; D023041:Xenograft Model Antitumor Assays
chemical_list: D014750:Vincristine; D003520:Cyclophosphamide