Efficacy of Combined Photodynamic and Hyperthermic Therapy with a New Light Source in an in Vivo Osteosarcoma Tumor Model

Department of Oral and Maxillofacial Surgery, Faculty of Medicine, Mie University, Tsu, Japan.
Journal of Clinical Laser Medicine & Surgery 03/2004; 22(1):3-8. DOI: 10.1089/104454704773660903
Source: PubMed


In this study, we investigated the efficacy of Super Lizer (SL) as a new light source in photodynamic therapy (PDT) with hyperthermia in an in vivo osteosarcoma tumor model.
Nude mice in three study groups (PDT only, PDT with hyperthermia in low energy, and PDT with hyperthermia in high energy) and three control groups (no treatment, photosensitizer only, and hyperthermia only) were implanted subcutaneously with human osteosarcoma cells and injected with a photosensitizing hematoporphyrin derivative (HPD) at a total dose of 10 mg/kg, in all study groups and in control group 2. At 72 h after light treatment, mice were sacrificed.
The tumor volume growth rates in the heat-only (1.50) and PDT-only (1.40) groups were significantly lower than the growth rate in the no-treatment group (1.82). Further, the tumor volume growth rate in the PDT with hyperthermia in high-energy group (1.19) was significantly lower than in the heat- or PDT-only groups.
Although non-laser PDT, including SL-PDT, may be beneficial only in the treatment of superficial tumors because of limited light penetration, PDT combined with hyperthermia may extend the utility of PDT in antitumor treatment. The use of SL as a new light source in PDT may significantly advance antitumor therapy due to its simplicity, ease, and cost benefit.

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    • "PDT is becoming more widely applied for the diagnosis and treatment of malignant tumors. Recent experimental studies (43,44) have also revealed that PDT is a novel effective approach for treating malignancies such as osteosarcoma, Ewing’s sarcoma of the soft tissues and synovial sarcoma (SS). "
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    ABSTRACT: Photodynamic therapy (PDT) has clinical approval for use as a minimally invasive therapeutic procedure that is able to exert selective cytotoxic activity toward pathological cells, particularly malignant cells. Following a number of recent technological improvements, PDT has been widely applied to the diagnosis and treatment of malignancies, including lung, esophageal, gastrointestinal, bladder, prostate, head and neck, oral and skin cancer. Studies have shown that osteosarcoma is a malignant tumor afflicting young adults worldwide, and recently, the incidence of bone and soft-tissue malignant tumors has been shown to be increasing, so the use of PDT has become an area of focus for the diagnosis and treatment of musculoskeletal sarcoma.
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    ABSTRACT: Photodynamic therapy (PDT), following health agency approvals throughout the world for various cancers and other diseases, is slowly being accepted as a standard treatment to be added to the medical practitioner's armamentarium. This includes palliative treatments such as for obstructive esophageal and lung cancers as well as those intended for cure, early stage lung cancer, and actinic keratoses. A particularly new and important application is for the treatment of age-related macular degeneration (AMD), where PDT (Visudyne) has made a major impact on the outcome of this disease, the major cause of blindness in those over the age of 50. In the cancer field, while not yet approved (pending), the use of PDT in treatment of high-grade dysplasia (HGD) in Barrett's esophagus may well change how this disease is currently treated (often esophagectomy). Mechanistically, the recognition of apoptosis as an important mode of cell death following PDT and the critical role of the inflammatory process and immunity has only recently been recognized. This review updates the current and future role of PDT in cancer and other diseases.
    No preview · Article · Mar 2002 · Journal of Clinical Laser Medicine & Surgery
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    ABSTRACT: In the present study, we have investigated a combination of photodynamic therapy (PDT) using 5-aminolevulinic acid (ALA) and simultaneous hyperthermia (HT) on osteosarcoma (HOSM-1) cells, squamous cell carcinoma (KB) cells and fibroblasts (HF), including an assessment of the differences in the sensitivity of these cells to such treatment in vitro. The intracellular accumulation of protoporphyrin IX (PPIX) formed by metabolism of ALA in mitochondria and the influence of the treatment on the mitochondrial membrane potential were evaluated using flow cytometry. The antitumor effects of HT, PDT using ALA (ALA-PDT) and ALA-PDT combined with HT (PDT+HT) were determined by an MTT assay. Western blot analysis of the expression of heat shock protein 60 (Hsp60) and Hsp70 was performed to evaluate the mitochondrial stress caused by each treatment. The intracellular PPIX accumulation in HOSM-1 cells was about 2-fold higher than that in KB cells. An antitumor effect of ALA-PDT and PDT+HT was obtained in each cell line, and indicated a synergistic interaction of the combination therapy in tumor cells. A marked degree of depolarization of the mitochondrial membrane was observed in both tumor cell lines, and there was no marked difference in the degree of depolarization between the cell lines. Marked expression of Hsp60 was observed in HOSM-1 cells treated with PDT+ HT and ALA-PDT, but not in KB cells. Slightly increased expression of Hsp70 was observed for all treatments in both tumor cell lines. These results suggest that the antitumor effect of ALA-PDT therapy against malignant tumor cells is enhanced by simultaneous HT. Furthermore, the differences in sensitivity to these therapies between the two cell types may have occurred because PPIX was not effectively utilized in HOSM-1 cells, compared to its utilization in KB cells.
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