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Pre-clinical Evaluation of Tyrosine Kinase Inhibitors for Treatment of Acute Leukemia
Published on: September 18, 2013
Therapeutic effects of systemic photodynamic therapy in a leukemia animal model using A20 cells
Lan Ying Wen1, Su-Mi Bae, Heung-Jae Chun
1Cancer Research Institute of Medical Science, The Catholic University of Korea College of Medicine, 505 Banpodong, Seocho-ku, Seoul, 137-040, South Korea.
Abstract:
Photodynamic therapy (PDT) is attracting attention because of its noticeable inhibitory effects on the growth of dermatological and other solid tumors. Here, we studied the use of PDT in systemic diseases such as leukemia, lymphoma, and metastatic cancer, for which tumor formation areas cannot be clearly compartmentalized. We developed a systemic PDT method and examined its effect in a leukemia mouse model. Growth inhibition of A20 cells (H-2(d), murine B-lymphoma/leukemia, and Balb/c origin) induced by PDT/Photodithazine was evaluated by EZ-Cytox assay. After PDT, changes in cell morphology were assessed by light microscopy. Induction of apoptosis, as well as changes in the cell cycle, were assessed by fluorescence-activated cell sorting (FACS) analysis. A20 cells were injected into Balb/c mice through the tail veins, and PDT was performed. A total of 10 mg kg(-1) body weight of Photodithazine concentration was injected intravenously. After 5 min, micro photofibers (diameter, 200 μm) were inserted into the tail veins and irradiated at 1,200 J with a laser. PDT inhibited growth of A20 cells and resulted in marked morphological changes. PDT also induced apoptosis and G1 arrest. In a leukemia mouse model, systemic PDT increased the survival rate (p < 0.01). This is the first report of the effects of systemic PDT in a leukemia animal model. PDT has been applied only locally in most cases, for example to solid tumors. This study provides experimental evidence that systemic PDT could effectively be applied to systemic and spread tumors, for which tumor formation areas cannot clearly be determined.
Insights
Systemic photodynamic therapy (PDT) effectively inhibited leukemia cell growth and increased survival rates in a mouse model. This study demonstrates PDT
Area of Science:
- Oncology
- Biomedical Engineering
- Photomedicine
Background:
- Photodynamic therapy (PDT) shows promise for solid tumors.
- Systemic diseases like leukemia pose challenges for localized treatments.
- Novel approaches are needed for widespread or non-localized cancers.
Purpose of the Study:
- To investigate the efficacy of a systemic photodynamic therapy (PDT) method.
- To evaluate PDT's effects on leukemia cells and in a leukemia mouse model.
- To explore PDT as a treatment for systemic and metastatic cancers.
Main Methods:
- Developed and applied a systemic PDT method using Photodithazine in a leukemia mouse model.
- Assessed A20 leukemia cell growth inhibition via EZ-Cytox assay.
- Analyzed cell morphology, apoptosis, and cell cycle changes using microscopy and FACS analysis.
- Administered Photodithazine intravenously and used micro photofibers for laser irradiation in tail veins.
Main Results:
- Systemic PDT significantly inhibited A20 leukemia cell growth.
- PDT induced notable changes in cell morphology and promoted apoptosis.
- Cell cycle analysis revealed G1 arrest following PDT treatment.
- The leukemia mouse model showed a significant increase in survival rate (p < 0.01) after systemic PDT.
Conclusions:
- Systemic PDT is effective in inhibiting leukemia cell growth and proliferation.
- PDT induces apoptosis and cell cycle arrest in leukemia cells.
- This study provides the first evidence of systemic PDT's efficacy in a leukemia animal model.
- Systemic PDT offers a potential therapeutic strategy for systemic and metastatic cancers where tumors are not clearly defined.
