title: A study of pipeline drugs in neuroendocrine tumors.
abstract: OBJECTIVE
  Inhibition of neovessel development can stabilize tumor growth. A rapid in vitro method that can evaluate the effectiveness of anti-angiogenic drugs would aid in drug development. We tested a series of investigational agents to determine their ability to inhibit angiogenesis in our in vitro human angiogenesis model.
  
  
  METHODS
  A total of 74 neuroendocrine tumors were tested with five therapeutic agents for anti-angiogenic activity. Angiogenic responses were assessed visually and the percent of tumor explants that developed an angiogenic response was determined. The extent of neovessel growth was rated using a validated semi-quantitative visual scale. Analysis of variance was used to compare treatment outcome results to control values for these angiogenic parameters.
  
  
  RESULTS
  Vatalanib (2 × 10(-5) M) and patupilone (1 × 10(-8) M) were highly effective inhibitors of human tumor angiogenesis (mean overall angiogenic response for drug versus control 1.3 vs. 5.9 and 0.2 vs. 5.2, respectively) and were statistically significant at p <0.0001. Imatinib (2.5 × 10(-6) M) and everolimus (1 × 10(-8) M) were also effective (mean overall angiogenic response for drug versus control 2.2 vs. 5.9 and 4.5 vs. 5.9, respectively), and these were also statistically significant at p <0.0001. Pasireotide (1 × 10(-8) M) had no effect on angiogenesis (mean overall angiogenic response for drug vs. control 5.5 vs. 5.2).
  
  
  CONCLUSIONS
  Significant differences in angiogenic response to test drugs were noted in this neuroendocrine patient population. In vitro screening of a large series of fresh human tumors may be a cost-effective way to select drugs for continued clinical development.
authors.affiliation: Department of Surgery, Louisiana State University Health Sciences Center, New Orleans, LA 70112, USA. cantho@lsuhsc.edu
authors.forename: Catherine T
authors.initials: CT
authors.lastname: Anthony
authors.forename: Juan G
authors.initials: JG
authors.lastname: Bastidas
authors.forename: Jessica L
authors.initials: JL
authors.lastname: Thomson
authors.forename: John
authors.initials: J
authors.lastname: Lyons
authors.forename: James M
authors.initials: JM
authors.lastname: Lewis
authors.forename: Joshua E
authors.initials: JE
authors.lastname: Schwimer
authors.forename: Peter
authors.initials: P
authors.lastname: Casey
authors.forename: Jennifer
authors.initials: J
authors.lastname: Abadie
authors.forename: Daniel J
authors.initials: DJ
authors.lastname: Frey
authors.forename: Yi-Zarn
authors.initials: YZ
authors.lastname: Wang
authors.forename: J Philip
authors.initials: JP
authors.lastname: Boudreaux
authors.forename: Eugene A
authors.initials: EA
authors.lastname: Woltering
mesh_terms: D020533:Angiogenesis Inhibitors / Q000494:pharmacology*; D004354:Drug Screening Assays, Antitumor; D006801:Humans; D066298:In Vitro Techniques; D009389:Neovascularization, Pathologic; D018358:Neuroendocrine Tumors / Q000098:blood supply*
chemical_list: D020533:Angiogenesis Inhibitors