Abstract

The overall goal of this project is to use in vivo NMR spectroscopy and micro-electrode measurements to provide detailed knowledge of the dynamic response of transplanted adenocarcinoma in C3H/HeJ mice to phototherapy using chemiluminescence photoactivation of hematoporphyrin derivative, (Photofrin II). This information, together with results of related independent studies of photo-therapy using external photoactivation, will be used to elucidate the mechanism of action for hematoporphyrin - chemiluminescence phototherapy. This project had the following specific aims: 1) determine the temporal relationship between the changes in tumor blood flow, P-31 NMR metabolic characteristics, and intralesional p02 and pH which are induced by hematoporphyrin-chemiluminescence phototherapy; 2) compare the effects of phototherapy using chemiluminescence photoactivation with the effects of phototherapy using external photoactivation, as determined in related independent studies; 3) evaluate the effect of tumor size on both the physiological response and the therapeutic response of tumors treated with phototherapy using either chemiluminescence or external photoactivation; and 4) examine the relationship between therapeutic response to phototherapy and the tumor NMR metabolic characteristics before and after phototherapy as a function of the dose of both chemiluminescence and external light photoactivation. In vivo P-31 surface coil NMR spectroscopy will be used to study tumor metabolic characteristics in response to activation by hematoporphyrin chemiluminescence. F-19 NMR in conjunction with fluorinated vascular markers (e.g., perfluorocarbon blood substitutes) will be used to provide a measure of relative rates of blood flow in treated tumors. Microelectrode measurements will be carried out to evaluate the distribution of the P02 and pH within the tumor. The combination to these techniques will allow us to assess the temporal relationship of P-31 metabolic characteristics, blood flow, and intralesional pH and p02.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Research Program Projects (P01)
Project #
5P01CA043892-03
Application #
3817054
Study Section
Project Start
Project End
Budget Start
Budget End
Support Year
3
Fiscal Year
1989
Total Cost
Indirect Cost

  Institution

Name
Henry Ford Health System
Department
Type
DUNS #
City
Detroit
State
MI
Country
United States
Zip Code
48202

  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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