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Antiangiogenic treatment with the three thrombospondin-1 type 1 repeats recombinant protein in an orthotopic human pancreatic cancer model.

Publication ,  Journal Article
Zhang, X; Galardi, E; Duquette, M; Delic, M; Lawler, J; Parangi, S
Published in: Clin Cancer Res
March 15, 2005

PURPOSE: This study investigates the antiangiogenesis and antitumor efficacy of a recombinant protein composed of the three type 1 repeats (3TSR) of thrombospondin-1 in an orthotopic human pancreatic cancer model and provides useful preclinical data for pancreatic cancer treatment. EXPERIMENTAL DESIGN: Human pancreatic cancer cells (AsPC-1) were injected into the pancreas of severe combined immunodeficient mice. The animals were treated with 3TSR (3 mg per kg per day) or PBS for 3 weeks. Subsequently, the effects of 3TSR on tumor growth, microvessel density, cancer cell proliferation, apoptosis, and endothelial cell apoptosis were analyzed. The in vitro effects of 3TSR on human pancreatic cancer cells were also studied. RESULTS: 3TSR treatment significantly reduced angiogenesis and tumor growth of orthotopic pancreatic cancer. 3TSR-treated mice had a 69% reduction in tumor volume (316.6 +/- 79.3 versus 1,012.2 +/- 364.5 mm(3); P = 0.0001), and a significant increase in tumor necrotic area. After 3TSR treatment, both the vessel number and average microvessel size were significantly decreased, and microvessel density was decreased from 8.0% to 3.7% (P < 0.0001). The apoptotic rate of tumoral endothelial cells in 3TSR-treated tumors increased to 14.7% comparing to 4.2% in control tumors (P < 0.0001). 3TSR showed no direct effects on pancreatic cancer cell proliferation or apoptosis either in vivo or in vitro. CONCLUSION: 3TSR, a domain of a natural occurring angiogenesis inhibitor, showed potent therapeutic effect in pancreatic cancer by inhibiting tumor angiogenesis and may prove to be a promising agent for clinical pancreatic cancer treatment.

Duke Scholars

Published In

Clin Cancer Res

DOI

ISSN

1078-0432

Publication Date

March 15, 2005

Volume

11

Issue

6

Start / End Page

2337 / 2344

Location

United States

Related Subject Headings

  • Xenograft Model Antitumor Assays
  • Tumor Cells, Cultured
  • Treatment Outcome
  • Thrombospondin 1
  • Repetitive Sequences, Nucleic Acid
  • Recombinant Proteins
  • Pancreatic Neoplasms
  • Oncology & Carcinogenesis
  • Neovascularization, Pathologic
  • Mice, SCID
 

Citation

APA
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ICMJE
MLA
NLM
Zhang, X., Galardi, E., Duquette, M., Delic, M., Lawler, J., & Parangi, S. (2005). Antiangiogenic treatment with the three thrombospondin-1 type 1 repeats recombinant protein in an orthotopic human pancreatic cancer model. Clin Cancer Res, 11(6), 2337–2344. https://doi.org/10.1158/1078-0432.CCR-04-1900
Zhang, Xuefeng, Eric Galardi, Mark Duquette, Marko Delic, Jack Lawler, and Sareh Parangi. “Antiangiogenic treatment with the three thrombospondin-1 type 1 repeats recombinant protein in an orthotopic human pancreatic cancer model.Clin Cancer Res 11, no. 6 (March 15, 2005): 2337–44. https://doi.org/10.1158/1078-0432.CCR-04-1900.
Zhang X, Galardi E, Duquette M, Delic M, Lawler J, Parangi S. Antiangiogenic treatment with the three thrombospondin-1 type 1 repeats recombinant protein in an orthotopic human pancreatic cancer model. Clin Cancer Res. 2005 Mar 15;11(6):2337–44.
Zhang, Xuefeng, et al. “Antiangiogenic treatment with the three thrombospondin-1 type 1 repeats recombinant protein in an orthotopic human pancreatic cancer model.Clin Cancer Res, vol. 11, no. 6, Mar. 2005, pp. 2337–44. Pubmed, doi:10.1158/1078-0432.CCR-04-1900.
Zhang X, Galardi E, Duquette M, Delic M, Lawler J, Parangi S. Antiangiogenic treatment with the three thrombospondin-1 type 1 repeats recombinant protein in an orthotopic human pancreatic cancer model. Clin Cancer Res. 2005 Mar 15;11(6):2337–2344.

Published In

Clin Cancer Res

DOI

ISSN

1078-0432

Publication Date

March 15, 2005

Volume

11

Issue

6

Start / End Page

2337 / 2344

Location

United States

Related Subject Headings

  • Xenograft Model Antitumor Assays
  • Tumor Cells, Cultured
  • Treatment Outcome
  • Thrombospondin 1
  • Repetitive Sequences, Nucleic Acid
  • Recombinant Proteins
  • Pancreatic Neoplasms
  • Oncology & Carcinogenesis
  • Neovascularization, Pathologic
  • Mice, SCID