Abstract

The objective of this proposal is to enhance the treatment of brain tumor with PDT. We have identified two methods to increase the efficacy of PDT to selectively kill brain tumor relative to normal brain. Photofrin administered encapsulated in a liposome and photofrin administered in conjunction with buthionine sulfoximide (BSO) (a glutathione inhibitor) significantly increases the PDT toxicity to tumor cells. In this project, we will develop, implement and optimize these con-PDT treatment methods of enhancing the PDT of brain tumor and investigate biophysical mechanisms responsible for this therapeutic enhancement.
Aim A: To measure the relative increase in therapeutic efficacy of photodynamic therapy in experimental brain tumor in rat treated with Photofrin encapsulated in a liposome (Photofrin-liposome) as the photosensitizing agent compared to Photofrin in a dextrose vehicle (Photofrin-dextrose) as the photosensitizing agent. Hypothesis A: The enhancement of PDT in the treatment of brain tumor with Photofrin-liposome when compared to Photofrin-dextrose is attributed to alterations of the pharmacokinetics and the intracellular localization of Photofrin.
Aim B: To measure the relative increase in therapeutic efficacy of photodynamic therapy in experimental brain tumor in rat treated with Photofrin by using buthionine sulfoximide (BSO) as an adjuvant to PDT. Hypothesis B: Administration of BSO decreases the level of gluthione in brain tumor tissue and therefore augments the intensity of brain tumor destruction with PDT. We expect that the optimization of these methods of enhancement of PDT destruction of brain tumor will find application in the clinic and may direct augmentation of human brain tumor treatment.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Research Program Projects (P01)
Project #
5P01CA043892-11
Application #
6300272
Study Section
Project Start
2000-01-01
Project End
2000-12-31
Budget Start
1998-10-01
Budget End
1999-09-30
Support Year
11
Fiscal Year
2000
Total Cost
$170,721
Indirect Cost

  Institution

Name
Healthone Alliance
Department
Type
DUNS #
098407869
City
Denver
State
CO
Country
United States
Zip Code
80203

  Publications

Wang, Luo-Wei; Huang, Zheng; Lin, Han et al. (2013) Effect of Photofrin-mediated photocytotoxicity on a panel of human pancreatic cancer cells. Photodiagnosis Photodyn Ther 10:244-251
Lei, Tim C; Pendyala, Srinivas; Scherrer, Larry et al. (2013) Optical profiles of cathode ray tube and liquid crystal display monitors: implication in cutaneous phototoxicity in photodynamic therapy. Appl Opt 52:2711-7
Weston, Mark A; Patterson, Michael S (2011) Calculation of singlet oxygen dose using explicit and implicit dose metrics during benzoporphyrin derivative monoacid ring A (BPD-MA)-PDT in vitro and correlation with MLL cell survival. Photochem Photobiol 87:1129-37
Santra, Manoranjan; Zheng, Xuguang; Roberts, Cindi et al. (2010) Single doublecortin gene therapy significantly reduces glioma tumor volume. J Neurosci Res 88:304-14
Singh, Gurmit; Alqawi, Omar; Espiritu, Myrna (2010) Metronomic PDT and cell death pathways. Methods Mol Biol 635:65-78
Zheng, Xuguang; Jiang, Feng; Katakowski, Mark et al. (2009) ADAM17 promotes breast cancer cell malignant phenotype through EGFR-PI3K-AKT activation. Cancer Biol Ther 8:1045-54
Hong, Xin; Jiang, Feng; Kalkanis, Steven N et al. (2009) Intracellular free calcium mediates glioma cell detachment and cytotoxicity after photodynamic therapy. Lasers Med Sci 24:777-86
Santra, Manoranjan; Santra, Sutapa; Roberts, Cindi et al. (2009) Doublecortin induces mitotic microtubule catastrophe and inhibits glioma cell invasion. J Neurochem 108:231-45
Gullo, Francesca; Maffezzoli, Andrea; Dossi, Elena et al. (2009) Short-latency cross- and autocorrelation identify clusters of interacting cortical neurons recorded from multi-electrode array. J Neurosci Methods 181:186-98
Szalad, Alexandra; Katakowski, Mark; Zheng, Xuguang et al. (2009) Transcription factor Sp1 induces ADAM17 and contributes to tumor cell invasiveness under hypoxia. J Exp Clin Cancer Res 28:129

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