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Silencing of ferrochelatase enhances 5-aminolevulinic acid-based fluorescence and photodynamic therapy efficacy.

ABSTRACT: Recurrence of glioma frequently occurs within the marginal area of the surgical cavity due to invading residual cells. 5-Aminolevulinic acid (5-ALA) fluorescence-guided resection has been used as effective therapeutic modalities to improve discrimination of brain tumour margins and patient prognosis. However, the marginal areas of glioma usually show vague fluorescence, which makes tumour identification difficult, and the applicability of 5-ALA-based photodynamic therapy (PDT) is hampered by insufficient therapeutic efficacy in glioma tissues.To overcome these issues, we assessed the expression of ferrochelatase (FECH) gene, which encodes a key enzyme that catalyses the conversion of protoporphyrin IX (PpIX) to heme, in glioma surgical specimens and manipulated FECH in human glioma cell lines.Prominent downregulation of FECH mRNA expression was found in glioblastoma tissues compared with normal brain tissues, suggesting that FECH is responsible for PpIX accumulation in glioblastoma cells. Depletion of FECH by small interference RNA enhanced PpIX fluorescence after exposure to 5-ALA concomitant with increased intracellular PpIX accumulation in glioma cells. Silencing of FECH caused marked growth inhibition and apoptosis induction by PDT in glioma cells.These results suggest that knockdown of FECH is a potential approach to enhance PpIX fluorescent quality for optimising the subjective discrimination of vague fluorescence and improving the effect of 5-ALA-PDT.

SUBMITTER: Teng L

PROVIDER: S-EPMC3048207 | biostudies-literature | 2011 Mar

REPOSITORIES: biostudies-literature

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Silencing of ferrochelatase enhances 5-aminolevulinic acid-based fluorescence and photodynamic therapy efficacy.

Teng L L Nakada M M Zhao S-G SG Endo Y Y Furuyama N N Nambu E E Pyko I V IV Hayashi Y Y Hamada J-I JI

British journal of cancer 20110208 5

<h4>Background</h4>Recurrence of glioma frequently occurs within the marginal area of the surgical cavity due to invading residual cells. 5-Aminolevulinic acid (5-ALA) fluorescence-guided resection has been used as effective therapeutic modalities to improve discrimination of brain tumour margins and patient prognosis. However, the marginal areas of glioma usually show vague fluorescence, which makes tumour identification difficult, and the applicability of 5-ALA-based photodynamic therapy (PDT) ...[more]

PMID: 21304523

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Project description:BackgroundPhotodynamic therapy (PDT) is widely used as a treatment for actinic keratoses (AK), with new sunlight-based regimens proposed as alternatives to lamp-based treatments. Prescribing indoor daylight activation could help address the seasonal temperature, clinical supervision, and access variability associated with outdoor treatments.ObjectiveTo compare the AK lesion clearance efficacy of indoor daylight PDT treatment (30 min of 5-aminolevulinic acid (ALA) pre-incubation, followed by 2 h of indoor sunlight) versus a lamp-based PDT treatment (30 min of ALA preincubation, followed by 10 min of red light).MethodsA prospective clinical trial was conducted with 41 patients. Topical 10% ALA was applied to the entire treatment site (face, forehead, scalp). Patients were assigned to either the lamp-based or indoor daylight treatment. Actinic keratosis lesion counts were determined by clinical examination and recorded for pre-treatment, 1-month, and 6-month follow-up visits.ResultsThere was no statistical difference in the efficacy of AK lesion clearance between the red-lamp (1-month clearance = 57 ± 17%, 6-month clearance = 57 ± 20%) and indoor daylight treatment (1-month clearance = 61 ± 19%, 6-month clearance = 67 ± 20%). A 95% confidence interval of the difference of the means was measured between -4.4% and 13.4% for 1-month, and -2.2% and +23.6% for 6-month timepoints when comparing the indoor daylight to the red-lamp treatment, with a priori interval of equivalence of ±20%.LimitationsEnsuring an equivalent dose between the indoor and lamp treatment cohorts limited randomisation since it required performing indoor daylight treatments only during sunny days.ConclusionIndoor-daylight PDT provided equivalent AK treatment efficacy to a lamp-based regimen while overcoming temperature limitations and UV-block sunscreen issues associated with outdoor sunlight treatments in the winter.Clinical trial registrationClinicaltrials.gov listing: NCT03805737.

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Silencing of ferrochelatase enhances 5-aminolevulinic acid-based fluorescence and photodynamic therapy efficacy.

Publications

Silencing of ferrochelatase enhances 5-aminolevulinic acid-based fluorescence and photodynamic therapy efficacy.

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