• Journal of Photoscience
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• 제9권2호
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• pp.512-514
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• 2002

S-aminolevulinic acid (ALA) is a new kind drug used in photodynamic therapy. ALA-PDT have successfully used in superficial malignancies and some skin diseases. Here the effects of ALA-PDT were studied on leukemia cells and hepatoma cells to explore the application on different kind cancers. It was found from the fluorescence emission spectra, that after ALA incubation the sensitizer - protoporphyrin IX (PpIX) was endogenously produced in both leukemia and hepatoma cells. The fluorescence images showed that the PpIX distribute in cytoplasm. However the efficiency of ALA photodynamic inactivation to two cell lines was different. The leukemia cells were more sensitive for ALA-PDT than hepatoma cells, revealing that the ALA-PDT effect is cell line dependent. However by using ALA-Hexyl ester (He-ALA) instead of ALA, the cell photo-inactivation was improved. The PDT efficiency of He-ALA was 10 times high than that of ALA, showing He-ALA is a very promising drug in ALA-PDT.

• Asian Pacific Journal of Cancer Prevention
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• 제14권5호
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• pp.3023-3028
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• 2013

Objective: Photodynamic therapy (PDT ) is a promising modality for the treatment of various tumors. In order to assist in optimizing treatment, we applied 5-ALA/PDT in combination with low-dose cisplatin to evaluate cytotoxicity in Hela cells. Methods: Antiproliferative effects of 5-ALA/PDT and cisplatin, alone and in combination, were assessed using MTT assay. To examine levels of apoptosis, Hela cells treated with 5-ALA/PDT, and combination treatment were assessed with Annexin-V/PI by flow cytometry. To investigate the molecular mechanisms underlying alterations in cell proliferation and apoptosis, Western blot analysis was conducted to determine the expression of p53, p21, Bax and Bcl-2 proteins. Results: MTT assays indicated that combination treatment obviously decreased the viability of Hela cells compared to individual drug treatment. In addition, it was confirmed that exposure of Hela cells to 5-ALA/PDT in combination with low-dose cisplatin resulted in more apoptosis in vitro. Synergistic anticancer activity was related to upregulation p53 expression and alteration in expression of p21, Bcl-2 and Bax. Conclusion: Our findings suggest that administration of 5-ALA/PDT in combination with the low-dose cisplatin may be an effective and feasible therapy for cervical cancer.

• Journal of Photoscience
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• 제9권2호
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• pp.509-511
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• 2002

In this study, we investigated apoptotic cell death induced by photodynamic therapy using 5-aminolaevulinic acid (ALA-PDT) in human promyelocytic leukemia cells (HL-60). ALA-PDT induced apoptosis in HL-60 cells as confirmed by DNA agarose gel electrophoresis and nuclear staining with Hoechst 33342. The apoptotic cell death was inhibited by addition of broad-spectrum caspase inhibitor Z-Asp-CH$_2$-DCB, indicating that the apoptotic cell death was induced in a caspase-dependent manner. Actually, western blotting analysis revealed that caspase-3 was processed as early as 1.5 h after ALA-PDT. Cytoplasmic cytochrome c released from mitochondria was detected by western blotting. However, inhibitor of caspase-9, a cysteine protease located in the downstream of cytochrome c release, was not able to reduce the apoptotic cell death. Therefore, the mitochondrial apoptotic pathway was not involved in the ALA-PDT-induced apoptosis. On the other hand, it was found that ALA-PDT-induced apoptosis was clearly inhibited by pretreatment of caspase-8 inhibitor. These data suggest that caspase-8-mediated apoptotic pathway is important in ALA-PDT-induced cell death.

• Archives of Pharmacal Research
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• 제28권10호
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• pp.1111-1113
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• 2005

5-Aminolevulinic acid and its derivatives, which are known to affect the early diagnosis and treatment of cancer, have been synthesized. Simple methods for the synthesis of 5-aminole-vulinic acid (ALA), a precursor of porphyrins, have been developed in our laboratory for use in studies on the biosynthesis of porphyrins.

• Asian Pacific Journal of Cancer Prevention
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• 제17권2호
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• pp.775-779
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• 2016

Background: The current study examined the effectiveness of concurrent therapy using photodynamic therapy (PDT) and clofibric acid (CA) to treat peritoneal carcinomatosis resulting from ovarian cancer. Materials and Methods: Nude rats were used to create a model of peritoneal carcinomatosis resulting from ovarian cancer and the effectiveness of PDT with 5-aminolevulinic acid methyl ester hydrochloride (methyl-ALA-PDT) was determined. The survival time of rats receiving that therapy was compared to the survival time of a control group. Rats with peritoneal carcinomatosis resulting from ovarian cancer were divided into 3 groups: a group that received debulking surgery (DS) alone, a group that received DS+methyl-ALA-PDT, and a group that received DS+methyl-ALA-PDT+CA. The survival time of the 3 groups was compared. Protoporphyrin, a metabolite of methyl-ALA, produces a photochemical action when activated by light. The level of protoporphyrin (the concentration) that reached organs in the abdomen was measured with HPLC. Results: Rats receiving methyl-ALA-PDT had a significantly longer survival time compared to the controls. Rats with peritoneal carcinomatosis that received DS+methyl-ALA-PDT+CA had a significantly longer survival time compared to the rats that received DS alone. Some of the rats that received concurrent therapy survived for a prolonged period. Protoporphyrin was highly concentrated in peritoneal metastases, but only small amounts reached major organs in the abdomen. PDT was not found to result in necrosis in the intestines. Conclusions: The results indicated that concurrent therapy consisting of PDT with methyl-ALA and CA is effective at treating peritoneal carcinomatosis resulting from ovarian cancer without damaging organs.

• 대한의생명과학회지
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• 제14권2호
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• pp.83-89
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• 2008

We have compared the antitumor effect of photodynamic therapy (PDT), using 5-aminolevulinic acid (ALA) as the photosensitizer, combined with cisplatin (CDDP) on AMC-HN3 human squamous cell carcinoma. AMC-HN3 cells were cultured and then incubated with various concentrations of CDDP and ALA. 632 nm diode laser was given at $6.0J/cm^2$ followed by incubation for 24 hours. The evaluation of cell viability was done by MTT assay. In vivo CDDP was injected intraperitoneally 24 hours prior to PDT. The anti-tumor effects of each treatment were measured by tumor volume change. Cell viability were 44.29% for the cisplatin-mediated chemotherapy group $(6.25{\mu}g/ml)$, 77.22% for ALA-PDT group, and 15.06% for the Combination therapy group. In vivo, the antitumor effect of photodynamic therapy was enhanced by combination of Cisplatin-mediated chemotherapy. Photodynamic therapy combined with administration of Cisplatin appears to enhance antitumor effect and to be a useful treatment modality.

• 대한임상검사과학회지
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• 제54권4호
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• pp.273-278
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• 2022

본 연구의 목적은 630 nm light emitting diode (LED)와 광감작제인 5-aminolevulinic acid (ALA)를 이용하여 병원균에 대한 광역학치료의 효과를 평가하는 것이었다. 1.5×10⁴ cells/mL의 세균 현탁액을 ALA 농도의 10, 5, 2.5, 1.25, 0.625 mg/mL로 희석하여 30분간 배양 후 LED (energy density 18 J/cm² )빛을 조사하였다 그 결과는 P. aeruginosa 에서는 광감작제를 처리하지 않은 군과 LED 빛만을 쬔 것은 각 평균 415, 245개가 형성되었다. 이에 반해 광역학 치료군인 ALA의 농도 10, 5, 2.5, 1.25 mg/mL에서 평균 109, 225, 297, 285개의 집락이 형성되었다. E. faecalis에서는 대조군인 광감작제를 처리하지 않은 군은 평균 8,750개의 집락을 형성하였고 빛만 쬔 군은 평균 8,000개의 집락을 형성하였다. 이에 반해 광역학 치료군인 ALA의 농도 5, 2.5, 1.25, 0.625 mg/mL 에서 평균 0, 2350, 4825, 7475개의 집락이 형성되었다. 결론적으로 그람음성균이 P. aeruginosa 보다 E. faecalis에서 더 좋은 광역학 치료효과를 보였으며, ALA와 630 nm LED를 이용한 광역학 치료의 가능성을 증명하였다.

• 한국임상수의학회지
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• 제37권1호
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• pp.1-8
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• 2020

Canine otitis externa is a common disorder in small animal practice with prevalence up to 20%. In a large percentage of cases, canine otitis externa is a chronic and recurrent disease also associated with drug-resistant bacteria that is difficult to treat with traditional antibiotics. Photodynamic therapy (PDT) is a new strategy to exterminate pathogenic microorganisms such as bacteria and fungi. The purpose of this study was to investigate the effectiveness of photodynamic therapy against canine otitis externa using three photosensitizer (PS); 5-Aminolevulinic acid (5-ALA) and Methyl aminolevulinic acid (MAL) with semiconductor laser diode (SLD, 635nm of wave length), Chlorophyll-lipoid complex (CLC) with light-emitting diode (LED, 660nm of wave length). After PDT, dogs showed improved Otitis Index Score (OTIS) in swelling, exudate, odor, and pain. A result of the cytology test revealed decrease of bacteria and malassezia count in the oil immersion field and colony forming units count. PDT was effective as a bacteriocide of methicillin-resistant Staphylococcus pseudintermedius (MRSP) and a fungicide of Malassezia pachydermatis. MAL and 5-ALA were more effective PS against canine otitis externa than CLC. These results suggest that PDT is a new strategy to exterminate pathogenic microorganisms such as bacteria and fungi. PDT can be considered as a new therapeutic approach for canine recurrent otitis externa and a countermeasure to drug resistance that is a disadvantage of traditional antibiotic and antifungal therapy.

• Journal of Photoscience
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• 제9권2호
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• pp.521-523
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• 2002

5-aminolevulinic acid (ALA) has been used to stimulate endogenous protoporphyrin IX (PpIX) in tumor and then initiate PDT. Recently, ALA-Hexyl ester (He-ALA) was found much effective than ALA on producing PpIX in cancer cells. To clarify the transportation mechanism of ALA and He-ALA, the detection of them is the important step. ALA and its derivatives all don't emit fluorescence, so the Raman spectroscopy was used here for the direct detection of ALA and He-ALA. The results showed that ALA and He-ALA have the common strong Raman peaks at 2930, 2950 CM$\^$-1/, due to the CH$_2$ vibration. The peak 3050 CM$\^$-1/ appeared in ALA spectrum can be attributed to OH vibration, while the peaks of 2860, 2900 CM$\^$-1/ in He-ALA spectrum were assigned as the modes of CH$_3$. This Raman spectral characteristic is consistence with the structure difference of He-ALA and ALA. Thus, Raman spectroscopy provides a new way to detect and distinguish ALA and He-ALA, and could be explored further in biology system.

• 한국임상수의학회지
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• 제31권1호
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• pp.66-69
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• 2014

Photodynamic therapy (PDT) is an effective method for infectious disease, but as yet, no clinical trial on otitis externa has been conducted in animals. This report describes 4 cases of PDT treatment on severe otitis externa in canine. Four canines were treated with various concentrations of 5-aminolevulinic acid hydrochloride (5-ALA) and with various J (second ${\times}$ power) and irradiated by light-emitting diode light source at 635 nm, respectively. After the PDT applications, canines incubated in the dark for 5 or 6 hr. All patients showed clinical resolution of otitis externa after PDT treatment at the dose of 0.16~0.3 g ALA and J (54~162 $J/cm^2$). On the basis of these findings, PDT can be considered to be a new therapeutic approach to severe otitis externa in canine.