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Antiangiogenic treatment with three thrombospondin-1 type 1 repeats versus gemcitabine in an orthotopic human pancreatic cancer model.

Publication ,  Journal Article
Zhang, X; Galardi, E; Duquette, M; Lawler, J; Parangi, S
Published in: Clin Cancer Res
August 1, 2005

PURPOSE: In this study, we investigated the antitumor efficacy of thrombospondin-1 three type 1 repeats (3TSR), the antiangiogenic domain of thrombospondin-1, in comparison and in combination with gemcitabine, in an orthotopic pancreatic cancer model. EXPERIMENTAL DESIGN: Human pancreatic cancer cells were injected into the pancreas of severe combined immunodeficient mice. The animals were treated with 3TSR, gemcitabine, 3TSR plus gemcitabine, or vehicle for 3 weeks. Subsequently, the effects of 3TSR and/or gemcitabine on tumor growth, tumor necrosis, microvessel density, cancer cell proliferation, apoptosis, and endothelial cell apoptosis were analyzed. RESULTS: After 3 weeks of treatment, 3TSR reduced tumor volume by 65%, and gemcitabine by 84%. Tumor volume was not statistically different between gemcitabine group and combinatorial treatment group. Extensive necrotic areas were observed in tumors from 3TSR-treated mice, whereas tumors from gemcitabine and combinatorially treated mice were less necrotic than control tumors. 3TSR reduced tumor microvessel density and increased tumor blood vessel endothelial cell apoptosis. In contrast, gemcitabine induced apoptosis and inhibited proliferation of cancer cells. CONCLUSION: 3TSR, the antiangiogenic domain of thrombospondin-1, showed comparable antitumor efficacy to gemcitabine in a human pancreatic cancer orthotopic mouse model. No synergistic effect was found when the two drugs were combined and possible reasons are discussed in detail. A delicate balance between normalization and excessive regression of tumor vasculature is important when initiating alternative combinatorial regimens for treatment of patients with pancreatic cancer.

Duke Scholars

Published In

Clin Cancer Res

DOI

ISSN

1078-0432

Publication Date

August 1, 2005

Volume

11

Issue

15

Start / End Page

5622 / 5630

Location

United States

Related Subject Headings

  • Time Factors
  • Thrombospondin 1
  • Recombinant Proteins
  • Protein Structure, Tertiary
  • Platelet Endothelial Cell Adhesion Molecule-1
  • Pancreatic Neoplasms
  • Oncology & Carcinogenesis
  • Neovascularization, Pathologic
  • Neoplasm Transplantation
  • Necrosis
 

Citation

APA
Chicago
ICMJE
MLA
NLM
Zhang, X., Galardi, E., Duquette, M., Lawler, J., & Parangi, S. (2005). Antiangiogenic treatment with three thrombospondin-1 type 1 repeats versus gemcitabine in an orthotopic human pancreatic cancer model. Clin Cancer Res, 11(15), 5622–5630. https://doi.org/10.1158/1078-0432.CCR-05-0459
Zhang, Xuefeng, Eric Galardi, Mark Duquette, Jack Lawler, and Sareh Parangi. “Antiangiogenic treatment with three thrombospondin-1 type 1 repeats versus gemcitabine in an orthotopic human pancreatic cancer model.Clin Cancer Res 11, no. 15 (August 1, 2005): 5622–30. https://doi.org/10.1158/1078-0432.CCR-05-0459.
Zhang X, Galardi E, Duquette M, Lawler J, Parangi S. Antiangiogenic treatment with three thrombospondin-1 type 1 repeats versus gemcitabine in an orthotopic human pancreatic cancer model. Clin Cancer Res. 2005 Aug 1;11(15):5622–30.
Zhang, Xuefeng, et al. “Antiangiogenic treatment with three thrombospondin-1 type 1 repeats versus gemcitabine in an orthotopic human pancreatic cancer model.Clin Cancer Res, vol. 11, no. 15, Aug. 2005, pp. 5622–30. Pubmed, doi:10.1158/1078-0432.CCR-05-0459.
Zhang X, Galardi E, Duquette M, Lawler J, Parangi S. Antiangiogenic treatment with three thrombospondin-1 type 1 repeats versus gemcitabine in an orthotopic human pancreatic cancer model. Clin Cancer Res. 2005 Aug 1;11(15):5622–5630.

Published In

Clin Cancer Res

DOI

ISSN

1078-0432

Publication Date

August 1, 2005

Volume

11

Issue

15

Start / End Page

5622 / 5630

Location

United States

Related Subject Headings

  • Time Factors
  • Thrombospondin 1
  • Recombinant Proteins
  • Protein Structure, Tertiary
  • Platelet Endothelial Cell Adhesion Molecule-1
  • Pancreatic Neoplasms
  • Oncology & Carcinogenesis
  • Neovascularization, Pathologic
  • Neoplasm Transplantation
  • Necrosis