Award Date

5-2009

Degree Type

Thesis

Degree Name

Master of Science in Health Physics

Department

Health Physics and Diagnostic Sciences

First Committee Member

Steen J. Madsen, Chair

Second Committee Member

Phillip W. Patton

Third Committee Member

Ralf Sudowe

Graduate Faculty Representative

Mack D. Rubley

Number of Pages

89

Abstract

Despite continued efforts, glioblastoma multiforme (GBM) remains an incurable form of primary brain cancer. Surgical resection followed by radiation treatment and chemotherapy have been the most effective modalities in prolonging median survival time to 14 months. This research aims to study the response of two different cell culture models to a novel drug delivery method termed photochemical internalization (PCI). PCI is a technique to improve the utilization of macromolecules (e.g. the chemotherapeutic drug bleomycin) in site-specific cancer therapy. This concept is based on the use of specially designed photosensitizers (e.g. aluminum phthalocyanine disulfonate; AlPcS 2a ) which preferentially localize in the membranes of endocytic vesicles.

The utility of PCI for treating malignant gliomas was investigated in vitro using: (1) F98 rat glioma monolayer cells, and (2) biopsy-derived human glioma spheroids. For both in vitro systems, PCI was found to interact in a synergistic manner resulting in significant toxicity. For example, the combination of 1.5 J/cm2 photodynamic therapy (PDT) and 0.25 μg/mL bleomycin resulted in approximately 25% survival in F98 rat glioma cells while only 35% of human glioma spheroids were observed to be growing two weeks post treatment. Overall, the degree of synergism was found to be less pronounced in the spheroid model. Collectively, the results show that AlPcS 2a -mediated PCI can be used to enhance the efficacy of chemotherapeutic agents such as bleomycin in malignant gliomas.

Keywords

Biophysics; Bleomycin; Brain--Cancer--Treatment; Chemotherapy; Glioblastoma multiforme; Medical sciences

Disciplines

Chemicals and Drugs | Medicine and Health Sciences | Oncology

Language

English

Comments

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