Total Tumor Cell Elimination with Minimum Damage to Normal Tissues in Musculoskeletal Sarcomas following Photodynamic Therapy with Acridine Orange

Kusuzaki, Katsuyuki; Aomori, Katsuhiro; Suginoshita, Takehiko; Minami, Ginjorou; Takeshita, Hideyuki; Murata, Hiroaki; Hashiguchi, Shin; Ashihara, Tsukasa; Hirasawa, Yasusuke

doi:10.1159/000012156

Cited by 47 publications

(56 citation statements)

References 19 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The reduced recurrence rate and preservation of function that we observed with high irradiation doses agree with reports that recurrence rates were reduced to 23% with PDT treatment compared with 80% with control treatment, and that function was preserved (Kusuzaki et al, 2000). All of the recurrences after high-dose PDT treatment that we observed were near the surgical margins, which suggests that selecting a high dose of irradiation to more fully clear the deep tumor cells may reduce the chance of recurrence from residual tumor tissue.…”

Section: Discussionsupporting

confidence: 90%

Benzochloroporphyrin Derivative Induced Cytotoxicity and Inhibition of Tumor Recurrence During Photodynamic Therapy for Osteosarcoma

Gong

Sun²,

Hu³

et al. 2013

Asian Pacific Journal of Cancer Prevention

View full text Add to dashboard Cite

Photodynamic therapy (PDT) is a promising cancer treatment modality that uses dye-sensitized photooxidation of biologic matter in target tissue. This study explored effects of the photosensitizer BCPD-17 during PDT for osteosarcoma. LM-8 osteosarcoma cells were treated with BCPD-17 and cell viability after laser irradiation was assessed in vitro with the 3-(4, 5-dimethylthiazol-2-yl)-2, 5-diphenyltetrazolium bromide assay. The effects of BCPD-17 during PDT recurrence were then examined on tumor-bearing mice in vivo. BCPD-17 had dosedependent cytotoxic effects on LM-8 osteosarcoma cells after laser irradiation which also had energy-dependent effects on the cells. The rate of local recurrence was reduced when marginal resection of mice tumors was followed by BCPD-17-mediated PDT. Our results indicated BCPD-17-mediated PDT in combination with marginal resection of tumors is a potentially new effective treatment for osteosarcoma.

show abstract

Section: Discussionsupporting

confidence: 90%

Benzochloroporphyrin Derivative Induced Cytotoxicity and Inhibition of Tumor Recurrence During Photodynamic Therapy for Osteosarcoma

Gong

Sun²,

Hu³

et al. 2013

Asian Pacific Journal of Cancer Prevention

View full text Add to dashboard Cite

show abstract

“…In an in-vivo study carried out using a mouse osteosarcoma model, tumor growth was significantly inhibited by AO injection at 10 mg/kg into the peritoneum followed by light illumination of the tumor. This result suggested the potential usefulness of AO for photodynamic therapy in patients with musculoskeletal sarcomas [20][21][22].…”

Section: Ao-pdt and Ao-rdtmentioning

confidence: 71%

“…Therefore, the tumors could be clearly visualized by fluorescence under the fluorescence surgical microscope equipped with a high resolution CCD camera (fluorovisualization effect) ( Figure 8) [18,[20][21]. Even small lesions, such as multiple pulmonary metastases from mouse osteosarcoma, measuring less than 1 mm of diameter can be easily detected by the emitted fluorescence ( Figure 9).…”

Section: Selective Accumulation Of Ao In Mouse Osteosarcoma Cells In mentioning

confidence: 99%

“…On the other hand, the tumor excluded AO more slowly, the dye remaining in the tumor, even after two hours. Therefore, AO is retained for longer periods of time in the tumors than in the muscles [18,21].…”

Section: Selective Accumulation Of Ao In Mouse Osteosarcoma Cells In mentioning

confidence: 99%

“…We also demonstrated that AO exerts selective cytocidal effects against sarcoma cells both in vitro and in vivo after illumination with visible light or irradiation of low-dose X-rays. It is available clinically for photodynamic therapy (PDT) [16][17][18][19][20][21] or radiodynamic therapy (RDT) [22][23].…”

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Intraoperative Photodynamic Surgery (iPDS) with Acridine Orange for Musculoskeletal Sarcomas

Kusuzaki¹,

Matsubara²,

Satonaka³

et al. 2014

Cureus

Self Cite

View full text Add to dashboard Cite

We recently established the new limb salvage modality of acridine orange (AO) therapy (AOT), in an attempt to develop minimally invasive limb salvage surgery with minimal damage of normal tissues and a low risk of local recurrence. The treatment modality consists of intraoperative photodynamic surgery (iPDS) and photodynamic therapy (iPDT), followed by postoperative radiodynamic therapy (RDT) using AO for patients with high-grade malignant musculoskeletal sarcomas. Clinical results have shown that the treatment is associated with a low risk of local recurrence, the risk being almost the same as that following conventional wide resection, and yields superior limb function as compared to that obtained after wide resection.In this review, we present the detailed mechanism of selective accumulation of AO in sarcomas, which is related to the acidic environment and lysosomal acidity of the tumor cells induced by cancer-specific glycolysis not involving the define tricarboxylic acid (TCA) cycle (Warburg's effect). We also describe the clinical uses of AOT and the procedure for intraoperative photodynamic surgery (iPDS) using local administration of AO.

show abstract

Molecular Entrapment in Thermophilic Ferritin for Nanoformulation in Photodynamic Therapy

Pasula

Kuniyil

Lim

2020

Advanced Therapeutics

View full text Add to dashboard Cite

Nanoformulation of therapeutic and diagnostic agents is beneficial as they accumulate at tumor sites due to enhanced permeability and retention effects. However, many in vitro studies performed on 2D cultures lack the realistic dimension of in vivo systems. In this work, a photosensitizer, acridine orange (AO), used in photodynamic therapy of cancer, is nanoformulated by entrapment in thermophilic ferritin. The efficacy is tested on 2D and 3D in vitro models and complemented with studies on the cellular uptake routes. Ferritin from the archaeon Archaeoglobus fulgidus (AfFtn) exhibits the unique property of divalent metal ion or ionic strength mediated assembly, making it an interesting nanocarrier for the entrapment of small molecules. The photosensitization and toxicity studies on 2D monolayers and 3D spheroid models of colorectal cancer cells show that AO loaded in AfFtn is functional. The killing efficiency in 2D monolayers reaches 50% while the growth of 3D spheroids is arrested after the first day with a subsequent 10% reduction of tumor diameter over the next 2 days. Results show that AO loaded AfFtn has better penetration ability than free AO alone in 3D spheroid models indicating that nanocage formulation provides for an efficient delivery vehicle into the tumor tissue.

show abstract

Total Tumor Cell Elimination with Minimum Damage to Normal Tissues in Musculoskeletal Sarcomas following Photodynamic Therapy with Acridine Orange

Cited by 47 publications

References 19 publications

Benzochloroporphyrin Derivative Induced Cytotoxicity and Inhibition of Tumor Recurrence During Photodynamic Therapy for Osteosarcoma

Benzochloroporphyrin Derivative Induced Cytotoxicity and Inhibition of Tumor Recurrence During Photodynamic Therapy for Osteosarcoma

Intraoperative Photodynamic Surgery (iPDS) with Acridine Orange for Musculoskeletal Sarcomas

Molecular Entrapment in Thermophilic Ferritin for Nanoformulation in Photodynamic Therapy

Contact Info

Product

Resources

About