title: Augmentation of chemotherapeutic infusion effect by TSU-68, an oral targeted antiangiogenic agent, in a rabbit VX2 liver tumor model.
abstract: OBJECTIVE
  This study was designed to investigate the in vivo effects of combination therapy with TSU-68 and chemotherapeutic infusion in a rabbit VX2 liver tumor model.
  
  
  METHODS
  This study was approved by the animal care committee at our institute. Three weeks before chemotherapeutic infusion, VX2 carcinoma was implanted into the livers of 32 rabbits. One week after chemotherapeutic infusion, vehicle was administered orally for 3 weeks in the control group (n = 16), and TSU-68 was administered orally at a daily dose of 200 mg/kg for 3 weeks in the treated group (n = 16). Computed tomography (CT) was performed before and 1, 2, 3, and 4 weeks after chemotherapeutic infusion. Tumor response was assessed according to the Response Evaluation Criteria in Solid Tumors (RECIST) on CT scan. The maximum thickness of viable tumor was measured on microscopic sections.
  
  
  RESULTS
  According to the RECIST, stable disease was observed in 9 (56%) rabbits and progressive disease in 7 (44%) in the control group, whereas partial response was observed in 1 (6%) rabbit and stable disease in 15 (94%) in the treated group. On pathologic examination, a viable lesion was present in 12 (75%) rabbits in the control group and in 6 (38%) rabbits in the treated group (P = 0.073). The mean maximum thickness of viable tumor in the treated group was significantly smaller than that in the control group (0.74 mm vs. 3.39 mm; P = 0.02).
  
  
  CONCLUSIONS
  Oral administration of TSU-68 augmented the effect of chemotherapeutic infusion in a rabbit VX2 liver tumor model.
authors.affiliation: Department of Radiology, Seoul National University College of Medicine, Institute of Radiation Medicine, Seoul National University Medical Research Center, and Clinical Research Institute, Seoul National University Hospital, #28 Yongon-dong, Chongno-gu, Seoul 110-744, Korea.
authors.forename: Hyo-Cheol
authors.initials: HC
authors.lastname: Kim
authors.forename: Jin Wook
authors.initials: JW
authors.lastname: Chung
authors.forename: Seung Hong
authors.initials: SH
authors.lastname: Choi
authors.forename: Seock-Ah
authors.initials: SA
authors.lastname: Im
authors.forename: Yasundo
authors.initials: Y
authors.lastname: Yamasaki
authors.forename: Suryoung
authors.initials: S
authors.lastname: Jun
authors.forename: Hwan Jun
authors.initials: HJ
authors.lastname: Jae
authors.forename: Jae Hyung
authors.initials: JH
authors.lastname: Park
mesh_terms: D000284:Administration, Oral; D020533:Angiogenesis Inhibitors / Q000494:pharmacology*; D000818:Animals; D004195:Disease Models, Animal; D004317:Doxorubicin / Q000008:administration & dosage / Q000494:pharmacology; D004359:Drug Therapy, Combination; D004998:Ethiodized Oil / Q000008:administration & dosage / Q000494:pharmacology; D007211:Indoles / Q000008:administration & dosage / Q000494:pharmacology*; D007262:Infusions, Intravenous; D008114:Liver Neoplasms, Experimental / Q000000981:diagnostic imaging / Q000188:drug therapy* / Q000473:pathology; D009389:Neovascularization, Pathologic / Q000000981:diagnostic imaging / Q000188:drug therapy* / Q000473:pathology; D000078183:Oxindoles; D011422:Propionates / Q000008:administration & dosage / Q000494:pharmacology*; D011758:Pyrroles; D011817:Rabbits; D018709:Statistics, Nonparametric; D014057:Tomography, X-Ray Computed
chemical_list: D020533:Angiogenesis Inhibitors; D007211:Indoles; D000078183:Oxindoles; D011422:Propionates; D011758:Pyrroles; D004998:Ethiodized Oil; D004317:Doxorubicin; C412603:orantinib