OtherBasic Science Investigations

Cooperative Effect of Radioimmunotherapy and Antiangiogenic Therapy with Thalidomide in Human Cancer Xenografts

Seigo Kinuya, Atsuhiro Kawashima, Kunihiko Yokoyama, Kiyoshi Koshida, Shota Konishi, Naoto Watanabe, Noriyuki Shuke, Hisashi Bunko, Takatoshi Michigishi and Norihisa Tonami
Journal of Nuclear Medicine August 2002, 43 (8) 1084-1089;

Article Figures & Data

Figures

  • FIGURE 1.
    FIGURE 1.

    Growth of LS180 colon cancer xenografts. Tumor volume is expressed as ratio relative to volume on day 0. ♦, Nontreated control; ▴, tumors treated with 200 mg/kg/d thalidomide; □, tumors treated with 4.63 MBq 131I-HPMS-1; ▪, tumors treated with thalidomide and 131I-HPMS-1; ○, tumors treated with 4.63 MBq 131I-A7; •, tumors treated with thalidomide and 131I-A7.

  • FIGURE 2.
    FIGURE 2.

    Changes in peripheral blood cell counts in mice. (A) RBCs; (B) WBCs; (C) platelets. ♦, Nontreated control; ▴, tumors treated with 200 mg/kg/d thalidomide; ○, tumors treated with 4.63-MBq RIT; •, tumors treated with thalidomide and RIT.

  • FIGURE 3.
    FIGURE 3.

    Body weight changes of mice. ♦, Nontreated control; ▴, tumors treated with 200 mg/kg/d thalidomide; ○, tumors treated with 4.63-MBq RIT; •, tumors treated with thalidomide and RIT.

  • FIGURE 4.
    FIGURE 4.

    Immunohistochemistry of tumor sections with an antifactor VIII antibody. Microvessel numbers in 200× field are 29.9 ± 2.5 in control tumor (A) and 8.30 ± 0.8 in tumor treated with thalidomide (B) (P < 0.0001).

  • FIGURE 5.
    FIGURE 5.

    In vitro proliferation assay of LS180 colon cancer cells in presence of increasing concentrations of thalidomide (n = 3). ▪, Without thalidomide; in presence of thalidomide: •, 0.1 μmol/L; ▴, 1 μmol/L; ♦, 5 μmol/L; □, 10 μ mol/L; ○, 50 μmol/L; ▵, 100 μmol/L.

  • FIGURE 6.
    FIGURE 6.

    Clonogenic assay of LS180 colon cancer cells exposed to x-ray radiation (n = 3). ♦, Control cells; cells pretreated with thalidomide for 24 h: ▪, 1 μmol/L; ▴, 10 μmol/L; ✖, 100 μmol/L.

Tables

  • TABLE 1

    Analysis of AUC of Growth Curves of Colon Cancer Xenografts After Initiation of Treatment

    TreatmentnAUC for 13 d
    Control582.5 ± 30.7
    Thalidomide1050.5 ± 15.5*
    HPMS-1558.6 ± 26.1†
    HPMS-1 + thalidomide643.0 ± 5.64‡
    A71029.6 ± 8.24§
    A7 + thalidomide1014.7 ± 7.04

    • ↵* P < 0.001 vs. control.

    • ↵† P < 0.05 vs. control.

    • ↵‡ Not significant vs. thalidomide or HPMS-1.

    • ↵§ P < 0.0001 vs. control and P < 0.01 vs. thalidomide.

    • ↵ P < 0.05 vs. A7.

    • Thalidomide = 200 mg/kg/d; HPMS-1 = 131I-irrelevant mAb (4.63 MBq); A7 = 131I-specific mAb (4.63 MBq).

      Data are expressed as mean ± SD.

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