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

Seigo Kinuya, MD1, Atsuhiro Kawashima, MD2, Kunihiko Yokoyama, MD1, Kiyoshi Koshida, MD3, Shota Konishi, MD1, Naoto Watanabe, MD4, Noriyuki Shuke, MD5, Hisashi Bunko, MD6, Takatoshi Michigishi, MD1 and Norihisa Tonami, MD1

1 Department of Biotracer Medicine, Kanazawa University Graduate School of Medical Sciences, Kanazawa, Japan
2 Department of Molecular and Cellular Pathology, Kanazawa University Graduate School of Medical Sciences, Kanazawa, Japan
3 Department of Integrative Cancer Therapy and Urology, Kanazawa University Graduate School of Medical Sciences, Kanazawa, Japan
4 Department of Radiology, Toyama Medical and Pharmaceutical University, Toyama, Japan
5 Department of Radiology, Asahikawa Medical College, Asahikawa, Japan
6 Medical Informatics, Kanazawa University Hospital, Kanazawa, Japan



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  		FIGURE 1. Growth of LS180 colon cancer xenografts. Tumor volume is expressed as ratio relative to volume on day 0. {diamondsuit}, Nontreated control; {blacktriangleup}, tumors treated with 200 mg/kg/d thalidomide; {square}, tumors treated with 4.63 MBq 131I-HPMS-1; {blacksquare}, tumors treated with thalidomide and 131I-HPMS-1; {circ}, tumors treated with 4.63 MBq 131I-A7; •, tumors treated with thalidomide and 131I-A7.

 


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  		FIGURE 2. Changes in peripheral blood cell counts in mice. (A) RBCs; (B) WBCs; (C) platelets. {diamondsuit}, Nontreated control; {blacktriangleup}, tumors treated with 200 mg/kg/d thalidomide; {circ}, tumors treated with 4.63-MBq RIT; •, tumors treated with thalidomide and RIT.

 


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  		FIGURE 3. Body weight changes of mice. {diamondsuit}, Nontreated control; {blacktriangleup}, tumors treated with 200 mg/kg/d thalidomide; {circ}, tumors treated with 4.63-MBq RIT; •, tumors treated with thalidomide and RIT.

 


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  		FIGURE 4. Immunohistochemistry of tumor sections with an antifactor VIII antibody. Microvessel numbers in 200x field are 29.9 ± 2.5 in control tumor (A) and 8.30 ± 0.8 in tumor treated with thalidomide (B) (P < 0.0001).

 


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  		FIGURE 5. In vitro proliferation assay of LS180 colon cancer cells in presence of increasing concentrations of thalidomide (n = 3). {blacksquare}, Without thalidomide; in presence of thalidomide: •, 0.1 µmol/L; {blacktriangleup}, 1 µmol/L; {diamondsuit}, 5 µmol/L; {square}, 10 µ mol/L; {circ}, 50 µmol/L; {triangleup}, 100 µmol/L.

 


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  		FIGURE 6. Clonogenic assay of LS180 colon cancer cells exposed to x-ray radiation (n = 3). {diamondsuit}, Control cells; cells pretreated with thalidomide for 24 h: {blacksquare}, 1 µmol/L; {blacktriangleup}, 10 µmol/L; , 100 µmol/L.

 




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