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Selective accumulation of ALA-induced PpIX and photodynamic effect in chemically induced hepatocellular carcinoma.

Otake M, Nishiwaki M, Kobayashi Y, Baba S, Kohno E, Kawasaki T, Fujise Y, Nakamura H - Br. J. Cancer (2003)

Bottom Line: Endogenously synthesised protoporphyrin IX (PpIX) following the administration of ALA is an effective photosensitiser for PDT.Based on these results, PDT was performed on HCC at 3 h after 500 mg x kg(-1) ALA administration before laser irradiation of 30 J per tumour.Antitumour effect was more evident in HCC than in the nontumoral tissue surrounding HCC.

View Article: PubMed Central - PubMed

Affiliation: Second Department of Internal Medicine, Hamamatsu University School of Medicine, Handayama 1-20-1, Hamamatsu, Shizuoka 431-3192, Japan. mamikoo@dream.com

ABSTRACT
The possibility of 5-aminolaevulinic acid-based photodynamic therapy (ALA-PDT) for liver cancer was investigated using a chemically induced hepatocellular carcinoma (HCC) model. Endogenously synthesised protoporphyrin IX (PpIX) following the administration of ALA is an effective photosensitiser for PDT. We determined the fluorescence intensity of PpIX in HCC and nontumoral tissue in the liver. 5-Aminolaevulinic acid was intravenously injected to male Fisher rats with HCC at a dose of 500 mg x kg(-1), and the fluorescence intensity in each tissue sample excised from liver was measured with a spectrofluorometer at 1, 3 and 6 h after administration. Fluorescence intensity was at a peak of 3 h after administration in both HCC and nontumoral tissue. The accumulation of PpIX in HCC was higher than that in the nontumoral tissue at 1 h (P<0.001) and 3 h (P<0.05) after ALA administration. Based on these results, PDT was performed on HCC at 3 h after 500 mg x kg(-1) ALA administration before laser irradiation of 30 J per tumour. Antitumour effect was more evident in HCC than in the nontumoral tissue surrounding HCC. These findings suggest the possibility to detect HCC by fluorescence and to treat HCC by light.

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Histological sections of the liver including HCC treated with 30 J per tumour 3 h after 500 mg kg−1 ALA administration. (A) Necrosis was evident in HCC (T), and the necrotic area was 9 mm in diameter and 8 mm in depth. Laser irradiation was performed from the topside. The arrows indicate the necrotic area. (B) Almost all the HCC is occupied with necrotic tissue. (C) On the contrary, necrosis was not evident in the nontumoral tissue (FAH) surrounding HCC. Scale: (A) HE, a bar represents 10 mm. (B,C) HE, a bar represents 0.1 mm.
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fig7: Histological sections of the liver including HCC treated with 30 J per tumour 3 h after 500 mg kg−1 ALA administration. (A) Necrosis was evident in HCC (T), and the necrotic area was 9 mm in diameter and 8 mm in depth. Laser irradiation was performed from the topside. The arrows indicate the necrotic area. (B) Almost all the HCC is occupied with necrotic tissue. (C) On the contrary, necrosis was not evident in the nontumoral tissue (FAH) surrounding HCC. Scale: (A) HE, a bar represents 10 mm. (B,C) HE, a bar represents 0.1 mm.

Mentions: Based on the above, PDT was performed on HCC at 3 h after 500 mg kg−1 ALA administration before 30 J per tumour laser irradiation. In all treated tumours, necrosis was evident at 24 h after ALA-PDT. A representative case with the largest tumour is shown in Figure 7Figure 7


Selective accumulation of ALA-induced PpIX and photodynamic effect in chemically induced hepatocellular carcinoma.

Otake M, Nishiwaki M, Kobayashi Y, Baba S, Kohno E, Kawasaki T, Fujise Y, Nakamura H - Br. J. Cancer (2003)

Histological sections of the liver including HCC treated with 30 J per tumour 3 h after 500 mg kg−1 ALA administration. (A) Necrosis was evident in HCC (T), and the necrotic area was 9 mm in diameter and 8 mm in depth. Laser irradiation was performed from the topside. The arrows indicate the necrotic area. (B) Almost all the HCC is occupied with necrotic tissue. (C) On the contrary, necrosis was not evident in the nontumoral tissue (FAH) surrounding HCC. Scale: (A) HE, a bar represents 10 mm. (B,C) HE, a bar represents 0.1 mm.
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Related In: Results  -  Collection

Show All Figures
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fig7: Histological sections of the liver including HCC treated with 30 J per tumour 3 h after 500 mg kg−1 ALA administration. (A) Necrosis was evident in HCC (T), and the necrotic area was 9 mm in diameter and 8 mm in depth. Laser irradiation was performed from the topside. The arrows indicate the necrotic area. (B) Almost all the HCC is occupied with necrotic tissue. (C) On the contrary, necrosis was not evident in the nontumoral tissue (FAH) surrounding HCC. Scale: (A) HE, a bar represents 10 mm. (B,C) HE, a bar represents 0.1 mm.
Mentions: Based on the above, PDT was performed on HCC at 3 h after 500 mg kg−1 ALA administration before 30 J per tumour laser irradiation. In all treated tumours, necrosis was evident at 24 h after ALA-PDT. A representative case with the largest tumour is shown in Figure 7Figure 7

Bottom Line: Endogenously synthesised protoporphyrin IX (PpIX) following the administration of ALA is an effective photosensitiser for PDT.Based on these results, PDT was performed on HCC at 3 h after 500 mg x kg(-1) ALA administration before laser irradiation of 30 J per tumour.Antitumour effect was more evident in HCC than in the nontumoral tissue surrounding HCC.

View Article: PubMed Central - PubMed

Affiliation: Second Department of Internal Medicine, Hamamatsu University School of Medicine, Handayama 1-20-1, Hamamatsu, Shizuoka 431-3192, Japan. mamikoo@dream.com

ABSTRACT
The possibility of 5-aminolaevulinic acid-based photodynamic therapy (ALA-PDT) for liver cancer was investigated using a chemically induced hepatocellular carcinoma (HCC) model. Endogenously synthesised protoporphyrin IX (PpIX) following the administration of ALA is an effective photosensitiser for PDT. We determined the fluorescence intensity of PpIX in HCC and nontumoral tissue in the liver. 5-Aminolaevulinic acid was intravenously injected to male Fisher rats with HCC at a dose of 500 mg x kg(-1), and the fluorescence intensity in each tissue sample excised from liver was measured with a spectrofluorometer at 1, 3 and 6 h after administration. Fluorescence intensity was at a peak of 3 h after administration in both HCC and nontumoral tissue. The accumulation of PpIX in HCC was higher than that in the nontumoral tissue at 1 h (P<0.001) and 3 h (P<0.05) after ALA administration. Based on these results, PDT was performed on HCC at 3 h after 500 mg x kg(-1) ALA administration before laser irradiation of 30 J per tumour. Antitumour effect was more evident in HCC than in the nontumoral tissue surrounding HCC. These findings suggest the possibility to detect HCC by fluorescence and to treat HCC by light.

Show MeSH
Related in: MedlinePlus