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Methods for Evaluation of a Snake Venom-Derived Disintegrin in Animal Models of Human Cancer

  • Stephen D. Swenson
  • Catalina Silva-Hirschberg
  • Francis S. MarklandEmail author
Protocol
Part of the Methods in Molecular Biology book series (MIMB, volume 2068)

Abstract

Integrin targeting has been shown to be an effective approach for anticancer therapy. We engineered a recombinant disintegrin, vicrostatin (VCN), that binds with high affinity and specificity to the Arg-Gly-Asp (RGD) class of integrins, including αvβ3, αvβ5, and α5β1, involved in tumor invasion and metastasis. We used three different delivery modalities to examine anticancer activity of VCN in mouse models of human ovarian cancer, glioma, and prostate cancer. A female mouse model was used to examine the treatment of established ovarian cancer (OC) using VCN delivered intraperitoneally (IP) weekly either in saline or impregnated in a viscoelastic gel. SKOV3luc cells (a human OC cell line) were directly injected IP into immunodeficient mice. We also examined the antitumor activity of radioiodinated VCN delivered intravenously in a human glioma model in nude mice. We evaluated the effectiveness of 131I-VCN in combination with the DNA alkylating agent temozolomide in limiting glioma growth. Finally, treatment of a bone metastatic model of human prostate cancer (PC) in immunodeficient mice was examined using a liposomal formulation of VCN (LVCN) delivered intravenously. Human PC cells were suspended in a solution of Matrigel and injected into the left tibia of immunodeficient mice. Diameters of both the left and right (control) tibias were measured by caliper repeatedly after VCN treatment was initiated.

Key words

Ovarian cancer Glioma Prostate cancer Integrins Disintegrins Animal models 

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Copyright information

© Springer Science+Business Media, LLC, part of Springer Nature 2020

Authors and Affiliations

  • Stephen D. Swenson
    • 1
    • 2
  • Catalina Silva-Hirschberg
    • 3
    • 4
  • Francis S. Markland
    • 1
    • 5
    Email author
  1. 1.Department of Biochemistry and Molecular Medicine, Keck School of MedicineUniversity of Southern CaliforniaLos AngelesUSA
  2. 2.Department of Neurological Surgery, Keck School of MedicineUniversity of Southern CaliforniaLos AngelesUSA
  3. 3.Department of Molecular Microbiology and Immunology, Keck School of MedicineUniversity of Southern CaliforniaLos AngelesUSA
  4. 4.Primary Speciality Center San LazaroSantiagoUSA
  5. 5.Norris Comprehensive Cancer Center, Keck School of MedicineUniversity of Southern CaliforniaLos AngelesUSA

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