title: Saporin toxins directed to basic fibroblast growth factor receptors effectively target human ovarian teratocarcinoma in an animal model.
abstract: BACKGROUND
  The antitumor activity of the chemical conjugate and recombinant forms of the mitotoxin basic fibroblast growth factor (bFGF) saporin (SAP) and the bFGF receptor-directed immunotoxin 11A8-SAP against human ovarian teratocarcinoma PA-1 was examined in athymic nude mice. Alternative administration schedules to prolong therapeutic efficacy were explored.
  
  
  METHODS
  Intravenous dosing (0.01-125 micrograms/kg) of chemical conjugate and recombinant bFGF-SAP or 11A8-SAP beginning 5 days after subcutaneous implantation of PA-1 cells was administered by i) weekly injection for 4 weeks, ii) continuous infusion for one week, or iii) daily injection five times a week for 4 weeks.
  
  
  RESULTS
  Weekly injections (31.25 micrograms/kg) of chemical conjugate bFGF-SAP or 11A8-SAP, the latter of which is 25% the molarity of the former, resulted in mean tumor volumes that were, respectively, 35% or 52% of controls (day 30) and 52% or 76% of controls (day 60). Chemical conjugate or recombinant bFGF-SAP administered weekly resulted in mean tumor volumes that were, respectively, 51% or 77% (0.5 microgram/kg) and 42% or 31% (50 micrograms/kg) of controls (day 30). A mean tumor volume of 35% of controls (day 30) and of 49% of controls (day 60) were observed in animals treated by constant infusion of chemical conjugate bFGF-SAP (125 micrograms/kg, total dose). Alternatively, tumors of animals receiving daily injections (125 micrograms/kg, total dose) exhibited a mean volume of 21% of controls (day 30) and prolonged growth inhibition as demonstrated by a mean tumor volume of 22% of controls (day 60).
  
  
  CONCLUSIONS
  These studies suggest a therapeutic potential for bFGF-receptor-directed saporin toxins in the treatment of ovarian teratocarcinoma and the importance of frequency of administration in achieving optimal tumor responses.
authors.affiliation: Department of Medicine, Roger Williams Medical Center, Providence, RI 02908, USA.
authors.forename: P
authors.initials: P
authors.lastname: Davol
authors.forename: J G
authors.initials: JG
authors.lastname: Beitz
authors.forename: M
authors.initials: M
authors.lastname: Mohler
authors.forename: W
authors.initials: W
authors.lastname: Ying
authors.forename: J
authors.initials: J
authors.lastname: Cook
authors.forename: D A
authors.initials: DA
authors.lastname: Lappi
authors.forename: A R
authors.initials: AR
authors.lastname: Frackelton
mesh_terms: D000818:Animals; D000972:Antineoplastic Agents, Phytogenic / Q000008:administration & dosage / Q000627:therapeutic use*; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D005260:Female; D006801:Humans; D000922:Immunotoxins / Q000008:administration & dosage; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D009699:N-Glycosyl Hydrolases; D010051:Ovarian Neoplasms / Q000188:drug therapy*; D010940:Plant Proteins / Q000008:administration & dosage / Q000627:therapeutic use*; D017468:Receptors, Fibroblast Growth Factor / Q000187:drug effects*; D054789:Ribosome Inactivating Proteins, Type 1; D000076985:Saporins; D018243:Teratocarcinoma / Q000188:drug therapy*; D014407:Tumor Cells, Cultured
chemical_list: D000972:Antineoplastic Agents, Phytogenic; D000922:Immunotoxins; D010940:Plant Proteins; D017468:Receptors, Fibroblast Growth Factor; D054789:Ribosome Inactivating Proteins, Type 1; D009699:N-Glycosyl Hydrolases; D000076985:Saporins