Enhancement of the effect of 5-aminolevulinic acid-based photodynamic therapy by simultaneous hyperthermia

Yanase, Shigeaki; Nomura, Junichi; Matsumura, Yoshihiko; Nagai, Koyu; Kinoshita, Machiko; Nakanishi, Hiroki; Ohnishi, Yasuhiro; Tokuda, T; Tagawa, Tetsuya

doi:10.3892/ijo.27.1.193

Cited by 18 publications

(22 citation statements)

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“…after PDT with various photosensitizers [46][47][48][49][50][51]. However, HSPs consist of large protein families and in our study we found that expression of members may be downregulated or upregulated after PDT with Foslipos.…”

Section: Discussionmentioning

confidence: 51%

Cellular and molecular effects of the liposomal mTHPC derivative Foslipos in prostate carcinoma cells in vitro

Gyenge

Hiestand

Graefe

et al. 2011

Photodiagnosis and Photodynamic Therapy

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BACKGROUND: Meso-tetra-hydroxyphenyl-chlorine (mTHPC) is among the most powerful photosensitizers available for photodynamic therapy (PDT). However, the mechanisms leading to cell death are poorly understood. We here focused on changes at DNA and RNA levels after treatment with the liposomal mTHPC derivative Foslipos in vitro. METHODS: After determination of darktoxicity, laser conditions and uptake kinetics, PC-3 prostate carcinoma cells were subjected to PDT with Foslipos, followed by assessment of cell numbers directly (TP0) or 1h (TP1), 2h (TP2), 5h (TP5) and 24h (TP24) after illumination. Nucleic acids had been extracted for evaluation of RNA amounts and integrity as well as for estimation of abasic sites as a measure for DNA damage. Furthermore, expression changes of 84 genes related to oxidative stress were investigated by quantitative polymerase chain reaction. RESULTS: Already at TP0, the number of dead cells was significantly higher after PDT versus controls and at TP24 more than 90% of cells had been destroyed. PDT resulted in a severe damage of both RNA and DNA. Gene expression analyses revealed an impact of PDT on pathways for oxidative and metabolic stress, heat shock, proliferation and carcinogenesis, growth arrest, inflammation, DNA repair and apoptosis signaling. CONCLUSIONS: Mechanisms of Foslipos-mediated PDT comprise a combination of acute and delayed lethal effects in PC-3 cells. The latter may include death processes initiated by nucleic acid damage, activation of stress and growth arrest genes in combination with a reduced capability to adequately cope with oxidative toxicity. Our results will help to better understand molecular photodynamic effects. AbstractBackground: Meso-tetra-hydroxyphenyl-chlorine (mTHPC) is among the most powerful

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Section: Discussionmentioning

confidence: 51%

Cellular and molecular effects of the liposomal mTHPC derivative Foslipos in prostate carcinoma cells in vitro

Gyenge

Hiestand

Graefe

et al. 2011

Photodiagnosis and Photodynamic Therapy

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“…Using the modified SL, we examined the effect of combination therapy of ALA-PDT and HT on human osteosarcoma in vitro (11). As a result, it was confirmed that the effect of ALA-PDT to kill cells would be significantly enhanced with simultaneous use of HT, and that one of the mechanisms of the synergistic interactions would be increase of mitochondrial damage.…”

Section: Introductionmentioning

confidence: 71%

“…On the other hand, 5-aminolevulinic acid (ALA), which has recently been used in clinical practice, is advantageous in that photosensitivity can be avoided, due to its excretion within 24 h, and that repeated administration is possible because of its short washout time. Therefore, in PDT with ALA (ALA-PDT) there are many advantages in that the same lesion can be treated repeatedly with no effect on subsequent treatment and the QOL is not impaired, due to decreased burden on the patient, such as post-treatment damage of the skin (3,11,12).…”

Section: -------------------------------------------------Table IV Smentioning

confidence: 99%

“…Furthermore, the effectiveness of HT combined with other therapies, especially radiotherapy, has been confirmed. Several studies have been performed with combination therapy of HT and PDT for malignant tumors and non-neoplastic diseases, suggesting the effectiveness of HT in combination therapy (11)(12)(13)(14)17,28,29).…”

Section: -------------------------------------------------Table IV Smentioning

confidence: 99%

“…Since ALA is administered locally, and has low permeability, production of protoporphyrin IX (PPIX) is limited to the surface and the treatment is considered to be ineffective for deep-seated nodular tumor (10). However, since ALA does not exhibit photosensitivity and causes no serious adverse effects, such as those observed in use of Photofrin (3), ALA can be used repeatedly at the same site, and is therefore considered to be useful in clinical practice (11,12). If combination therapy of ALA-PDT and HT is effective, not only for superficial diseases but for deep-seated diseases, broader treatment options will be available for neoplastic lesions, including malignant tumors.…”

Section: Introductionmentioning

confidence: 99%

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Synergistic interaction of 5-aminolevulinic acid-based photodynamic therapy with simultaneous hyperthermia in an osteosarcoma tumor model

Yanase¹,

Nomura²,

Matsumura³

et al. 2006

Int J Oncol

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Abstract. In this study, the effectiveness and mechanism of combination therapy of 5-aminolevulinic acid-based photodynamic therapy (ALA-PDT) with simultaneous hyperthermia (HT) on human-derived osteosarcoma in vivo were examined. A tumor model was prepared by subcutaneously implanting human osteosarcoma into nude mice and local injection of ALA was selected as the administration route. This study demonstrated that both ALA-PDT and the combination of ALA-PDT with HT exhibited significant inhibitory effects on tumor growth. In the group with high total energy, the growth inhibition rates of tumor were 52.3% in ALA-PDT, and 27.3% in ALA-PDT with simultaneous HT (PDT+HT), and the synergetic index was 1.76, demonstrating that the inhibitory effect on tumor growth in ALA-PDT was significantly increased by simultaneous use of HT. In the histological findings, after ALA-PDT, necrosis was observed in the area from the surface to a depth of 2 mm, and only a slight effect was confirmed in deeper layers. On the other hand, after PDT+HT, necrosis was observed in layers even deeper than 2 mm below the surface. Furthermore, based on the immunohistochemical findings of the expression of carbonic anhydrase IX, while weak expression of CAIX was observed after ALA-PDT in an area relatively close to the surface, a positive area extended to the deeper layers after PDT+HT compared with ALA-PDT. In conclusion, PDT+HT demonstrated a significant inhibitory effect on tumor growth of human-derived osteosarcoma, and a synergistic interaction of simultaneous HT. This suggests the possibility that ALA-PDT is useful, not only for the treatment of superficial tumors but also for deep-seated mesenchymal tumors, such as osteosarcoma. Furthermore, the mechanism of the synergistic interaction suggested that ALA-PDT was effective in the deep area of tumors due to the increase of blood flow by mild hyperthermia.

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Combined concurrent photodynamic and gold nanoshell loaded macrophage‐mediated photothermal therapies: An in vitro study on squamous cell head and neck carcinoma

et al. 2014

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Background and Objective Treatment modalities, such as hyperthermia and photodynamic therapy (PDT) have been used in the treatment of a variety of head and neck squamous cell carcinoma (HNSCC), either alone or as an adjuvant therapy. Macrophages loaded with gold nanoshells, which convert near-infrared light to heat, can be used as transport vectors for photothermal hyperthermia of tumors. The purpose of this study was to investigate the effects of combined macrophage mediated photothermal therapy (PTT) and PDT on HNSCC cells. Study Design/Materials and Methods Gold nanoshell loaded rat macrophages either alone or combined with human FaDu squamous cells in hybrid monolayers were subjected to PTT, PDT, or a simultaneous combination of the two light treatments. Therapies were given concurrently employing two laser light sources of λ = 670 nm (PDT) and λ = 810 nm (PTT), respectively. Results Significant uptake of gold nanospheres (AuNS) by rat alveolar macrophages was observed thus providing the rationale for their use as delivery vectors. Viability of the AuNS-loaded Ma was reduced to 35 and 12% of control values at an irradiance of 14 or 28 W/cm2 administered over a 5 minute period respectively. No significant cytotoxicity was observed for empty Ma for similar PTT exposure. AlPcS2a mediated PDT at a fluence level of 0.25 J/cm2 and PTT at 14 W/cm2 irradiance had little effect on cell viability for the FaDu/Ma (ratio 2:1) hybrid monolayers. In contrast, combined treatment reduced the cell viability to less than 40% at these same laser power settings. Conclusions The results of this study provide proof of concept for the use of macrophages as a delivery vector of AuNS for photothermal enhancement of the effects of PDT on squamous cell carcinoma. A significant synergy was demonstrated with combined PDT and PTT compared to each modality applied separately.

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Enhancement of the effect of 5-aminolevulinic acid-based photodynamic therapy by simultaneous hyperthermia

Cited by 18 publications

References 0 publications

Cellular and molecular effects of the liposomal mTHPC derivative Foslipos in prostate carcinoma cells in vitro

Cellular and molecular effects of the liposomal mTHPC derivative Foslipos in prostate carcinoma cells in vitro

Synergistic interaction of 5-aminolevulinic acid-based photodynamic therapy with simultaneous hyperthermia in an osteosarcoma tumor model

Combined concurrent photodynamic and gold nanoshell loaded macrophage‐mediated photothermal therapies: An in vitro study on squamous cell head and neck carcinoma

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