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Ischaemia-reperfusion injury in photodynamic therapy-treated mouse tumours.

Korbelik M, Sun J, Zeng H - Br. J. Cancer (2003)

Bottom Line: This burst of elevated XO activity declined rapidly, returning to the pretreatment levels within the next 30 min.The administration of XO inhibitor oxypurinol prevented this PDT-induced rise in XO activity.The oxypurinol treatment also decreased the extent of neutrophil accumulation in PDT-treated tumours and reduced the level of PDT-mediated cures.

View Article: PubMed Central - PubMed

Affiliation: British Columbia Cancer Agency, Vancouver, Canada. mkorbeli@bccancer.bc.ca

ABSTRACT
Prompted by the observation of ischaemia development during the treatment of tumours by photodynamic therapy (PDT) that is typically followed by a restoration of tumour blood flow and by the indications of secondary superoxide generation after PDT, we aimed in this study to obtain evidence of the induction of ischaemia-reperfusion (I/R) injury in PDT-treated tumours. Using subcutaneous mouse FsaR fibrosarcoma model and Photofrin-based PDT treatment, we have examined the activity of xanthine oxidase (XO, a key enzyme in the I/R injury development) in tumours before and after the therapy. Compared to the levels in nontreated tumours, there was a five-fold increase in the activity of this enzyme in tumours excised immediately after PDT. This burst of elevated XO activity declined rapidly, returning to the pretreatment levels within the next 30 min. Visible reflectance spectroscopy confirmed the occurrence of a PDT-induced strong but temporary reduction in tumour oxygenation. The administration of XO inhibitor oxypurinol prevented this PDT-induced rise in XO activity. The oxypurinol treatment also decreased the extent of neutrophil accumulation in PDT-treated tumours and reduced the level of PDT-mediated cures. These results demonstrate the induction of I/R injury in PDT-treated tumours, and show that it can contribute to the therapy outcome. Since I/R injury is a well-recognised proinflammatory insult, we suggest that its induction in PDT-treated tumours promotes the development of inflammatory response that has become established as a key element of the antitumour effect of PDT.

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The effect of PDT on XO activity in FsaR tumours. Subcutaneous FsaR tumours growing in C3H/HeN mice were treated by PDT (Photofrin 10 mg kg−1 followed 24 h later by 150 J cm−2). The tumours were excised either immediately post-PDT light treatment, or 15 or 30 min later. Their homogenates were used for the determination of XO activity as described in Materials and Methods. The samples were also prepared from nontreated tumours, tumours from mice not given Photofrin excised immediately after light treatment (light only), and those from mice given Photofrin 24 h earlier but not treated with light (Photofrin only). Bars represent s.d., n=4; *depicts statistically significant difference from the level in nontreated tumours (P<0.01).
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fig1: The effect of PDT on XO activity in FsaR tumours. Subcutaneous FsaR tumours growing in C3H/HeN mice were treated by PDT (Photofrin 10 mg kg−1 followed 24 h later by 150 J cm−2). The tumours were excised either immediately post-PDT light treatment, or 15 or 30 min later. Their homogenates were used for the determination of XO activity as described in Materials and Methods. The samples were also prepared from nontreated tumours, tumours from mice not given Photofrin excised immediately after light treatment (light only), and those from mice given Photofrin 24 h earlier but not treated with light (Photofrin only). Bars represent s.d., n=4; *depicts statistically significant difference from the level in nontreated tumours (P<0.01).

Mentions: The activity of XO determined in the homogenates of nontreated FsaR tumuors was around 7 mU h−1 mg−1 of tumour tissue (Figure 1Figure 1


Ischaemia-reperfusion injury in photodynamic therapy-treated mouse tumours.

Korbelik M, Sun J, Zeng H - Br. J. Cancer (2003)

The effect of PDT on XO activity in FsaR tumours. Subcutaneous FsaR tumours growing in C3H/HeN mice were treated by PDT (Photofrin 10 mg kg−1 followed 24 h later by 150 J cm−2). The tumours were excised either immediately post-PDT light treatment, or 15 or 30 min later. Their homogenates were used for the determination of XO activity as described in Materials and Methods. The samples were also prepared from nontreated tumours, tumours from mice not given Photofrin excised immediately after light treatment (light only), and those from mice given Photofrin 24 h earlier but not treated with light (Photofrin only). Bars represent s.d., n=4; *depicts statistically significant difference from the level in nontreated tumours (P<0.01).
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Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC2376337&req=5

fig1: The effect of PDT on XO activity in FsaR tumours. Subcutaneous FsaR tumours growing in C3H/HeN mice were treated by PDT (Photofrin 10 mg kg−1 followed 24 h later by 150 J cm−2). The tumours were excised either immediately post-PDT light treatment, or 15 or 30 min later. Their homogenates were used for the determination of XO activity as described in Materials and Methods. The samples were also prepared from nontreated tumours, tumours from mice not given Photofrin excised immediately after light treatment (light only), and those from mice given Photofrin 24 h earlier but not treated with light (Photofrin only). Bars represent s.d., n=4; *depicts statistically significant difference from the level in nontreated tumours (P<0.01).
Mentions: The activity of XO determined in the homogenates of nontreated FsaR tumuors was around 7 mU h−1 mg−1 of tumour tissue (Figure 1Figure 1

Bottom Line: This burst of elevated XO activity declined rapidly, returning to the pretreatment levels within the next 30 min.The administration of XO inhibitor oxypurinol prevented this PDT-induced rise in XO activity.The oxypurinol treatment also decreased the extent of neutrophil accumulation in PDT-treated tumours and reduced the level of PDT-mediated cures.

View Article: PubMed Central - PubMed

Affiliation: British Columbia Cancer Agency, Vancouver, Canada. mkorbeli@bccancer.bc.ca

ABSTRACT
Prompted by the observation of ischaemia development during the treatment of tumours by photodynamic therapy (PDT) that is typically followed by a restoration of tumour blood flow and by the indications of secondary superoxide generation after PDT, we aimed in this study to obtain evidence of the induction of ischaemia-reperfusion (I/R) injury in PDT-treated tumours. Using subcutaneous mouse FsaR fibrosarcoma model and Photofrin-based PDT treatment, we have examined the activity of xanthine oxidase (XO, a key enzyme in the I/R injury development) in tumours before and after the therapy. Compared to the levels in nontreated tumours, there was a five-fold increase in the activity of this enzyme in tumours excised immediately after PDT. This burst of elevated XO activity declined rapidly, returning to the pretreatment levels within the next 30 min. Visible reflectance spectroscopy confirmed the occurrence of a PDT-induced strong but temporary reduction in tumour oxygenation. The administration of XO inhibitor oxypurinol prevented this PDT-induced rise in XO activity. The oxypurinol treatment also decreased the extent of neutrophil accumulation in PDT-treated tumours and reduced the level of PDT-mediated cures. These results demonstrate the induction of I/R injury in PDT-treated tumours, and show that it can contribute to the therapy outcome. Since I/R injury is a well-recognised proinflammatory insult, we suggest that its induction in PDT-treated tumours promotes the development of inflammatory response that has become established as a key element of the antitumour effect of PDT.

Show MeSH
Related in: MedlinePlus