Antiangiogenic treatment enhances photodynamic therapy responsiveness in a mouse mammary carcinoma

A. Ferrario, K. F. Von Tiehl, N. Rucker, M. A. Schwarz, P. S. Gill, C. J. Gomer

Research output: Contribution to journalArticle

214 Citations (Scopus)

Abstract

Photodynamic therapy (PDT) is a promising cancer treatment that induces localized tumor destruction via the photochemical generation of cytotoxic singlet oxygen. PDT-mediated oxidative stress elicits direct tumor cell damage as well as microvascular injury within exposed tumors. Reduction in vascular perfusion associated with PDT-mediated microvascular injury produces tumor tissue hypoxia. Using a transplantable BA mouse mammary carcinoma, we show that Photofrin-mediated PDT induced expression of the hypoxia-inducible factor-1α (HIF-1α) subunit of the heterodimeric HIF-1 transcription factor and also increased protein levels of the HIF-1 target gene, vascular endothelial growth factor (VEGF), within treated tumors. HIF-1α and VEGF expression were also observed following tumor clamping, which was used as a positive control for inducing tissue hypoxia. PDT treatment of BA tumor cells grown in culture resulted in a small increase in VEGF expression above basal levels, indicating that PDT-mediated hypoxia and oxidative stress could both be involved in the overexpression of VEGF. Tumor-bearing mice treated with combined antiangiogenic therapy (IM862 or EMAP-II) and PDT had improved tumoricidal responses compared with individual treatments. We also demonstrated that PDT-induced VEGF expression in tumors decreased when either IM862 or EMAP-II was included in the PDT treatment protocol. Our results indicate that combination procedures using antiangiogenic treatments can improve the therapeutic effectiveness of PDT.

Original languageEnglish (US)
Pages (from-to)4066-4069
Number of pages4
JournalCancer Research
Volume60
Issue number15
StatePublished - 2000

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Photochemotherapy
Breast Neoplasms
Hypoxia-Inducible Factor 1
Vascular Endothelial Growth Factor A
Neoplasms
Therapeutics
Oxidative Stress
Dihematoporphyrin Ether
Singlet Oxygen
Wounds and Injuries
Clinical Protocols
Constriction
Blood Vessels
Transcription Factors
Perfusion

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

Ferrario, A., Von Tiehl, K. F., Rucker, N., Schwarz, M. A., Gill, P. S., & Gomer, C. J. (2000). Antiangiogenic treatment enhances photodynamic therapy responsiveness in a mouse mammary carcinoma. Cancer Research, 60(15), 4066-4069.

Antiangiogenic treatment enhances photodynamic therapy responsiveness in a mouse mammary carcinoma. / Ferrario, A.; Von Tiehl, K. F.; Rucker, N.; Schwarz, M. A.; Gill, P. S.; Gomer, C. J.

In: Cancer Research, Vol. 60, No. 15, 2000, p. 4066-4069.

Research output: Contribution to journalArticle

Ferrario, A, Von Tiehl, KF, Rucker, N, Schwarz, MA, Gill, PS & Gomer, CJ 2000, 'Antiangiogenic treatment enhances photodynamic therapy responsiveness in a mouse mammary carcinoma', Cancer Research, vol. 60, no. 15, pp. 4066-4069.
Ferrario A, Von Tiehl KF, Rucker N, Schwarz MA, Gill PS, Gomer CJ. Antiangiogenic treatment enhances photodynamic therapy responsiveness in a mouse mammary carcinoma. Cancer Research. 2000;60(15):4066-4069.
Ferrario, A. ; Von Tiehl, K. F. ; Rucker, N. ; Schwarz, M. A. ; Gill, P. S. ; Gomer, C. J. / Antiangiogenic treatment enhances photodynamic therapy responsiveness in a mouse mammary carcinoma. In: Cancer Research. 2000 ; Vol. 60, No. 15. pp. 4066-4069.
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