Kinetic fluorescence studies of 5-aminolaevulinic acid-induced protoporphyrin IX accumulation in basal cell carcinomas

Klinteberg, Claes af; Enejder, Annika; Wang, I; Andersson‐Engels, Stefan; Svanberg, Sune; Svanberg, Katarina

doi:10.1016/s1011-1344(99)00045-7

Cited by 75 publications

(52 citation statements)

References 32 publications

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“…Spectroscopic approaches similar to that presented here for separating PpIX fluorescence from endogenous tissue fluorescence has been previously reported by Klinteberg et al, 21 who used a similar technique for separation of PpIX fluorescence from tissue autofluorescence in photodynamic therapy of basal cell carcinoma. The endogenous fluorescence was removed by exponentially fitting the FAD fluorescence and then subtracting the FAD signal out to determine the photoproducts after photodynamic therapy.…”

Section: Discussionmentioning

confidence: 75%

“…Addition of exogenous ALA causes a preferential accumulation of protoporphyrin IX ͑PpIX͒ in cancerous cells when compared to normal cells. [15][16][17][18][19][20][21][22][23][24][25][26][27][28][29][30][31][33][34][35][36]39,40 PpIX is naturally produced by all nucleated cells during the heme cycle and meticulously controlled to prevent its natural accumulation. 37 This negative feedback system is thought to be modified in cancerous tissues due to ͑i͒ enzymatic defects that lead to an increase in protoporphyrinogen IX oxidase and/or ͑ii͒ reduced activity of ferrochelatase.…”

Section: Introductionmentioning

confidence: 99%

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Preferential accumulation of 5-aminolevulinic acid-induced protoporphyrin IX in breast cancer: a comprehensive study on six breast cell lines with varying phenotypes

et al. 2010

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Abstract. We describe the potential of 5-aminolevulinic acid ͑ALA͒-induced protoporphyrin IX ͑PpIX͒ fluorescence as a source of contrast for margin detection in commonly diagnosed breast cancer subtypes. Fluorescence intensity of PpIX in untreated and ALA-treated normal mammary epithelial and breast cancer cell lines of varying estrogen receptor expression were quantitatively imaged with confocal microscopy. Percentage change in fluorescence intensity integrated over 610-700 nm ͑attributed to PpIX͒ of posttreated compared to pretreated cells showed statistically significant differences between four breast cancer and two normal mammary epithelial cell lines. However, a direct comparison of post-treatment PpIX fluorescence intensities showed no differences between breast cancer and normal mammary epithelial cell lines due to confounding effects by endogenous fluorescence from flavin adenine dinucleotide ͑FAD͒. Clinically, it is impractical to obtain pre-and post-treatment images. Thus, spectral imaging was demonstrated as a means to remove the effects of endogenous FAD fluorescence allowing for discrimination between posttreatment PpIX fluorescence of four breast cancer and two normal mammary epithelial cell lines. Fluorescence spectral imaging of ALAtreated breast cancer cells showed preferential PpIX accumulation regardless of malignant phenotype and suggests a useful contrast mechanism for discrimination of residual cancer at the surface of breast tumor margins.

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Section: Discussionmentioning

confidence: 75%

Section: Introductionmentioning

confidence: 99%

Preferential accumulation of 5-aminolevulinic acid-induced protoporphyrin IX in breast cancer: a comprehensive study on six breast cell lines with varying phenotypes

et al. 2010

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“…Superficial BCC showed a maximum PpIX fluorescence 6 h post ALA application, whereas in nodular BCC the maximum occurred 2 to 4 h after the application. 45 This variability of the fluorescence intensity may be due to the duration of the ALA/MAL application time, the concentration of the ALA/ MAL cream, and/or the intensity of the illuminating light. There are various approaches to achieve robust tumor demarcation with derivation of novel unsupervised image segmentation methods that are not dependent on the variability of the fluorescence intensity, and LIF may be used for tumor demarcation, i.e., determination of the tumor boundaries.…”

Section: Pdd For Bccmentioning

confidence: 99%

Laser-induced fluorescence made simple: implications for the diagnosis and follow-up monitoring of basal cell carcinoma

et al. 2014

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Abstract. Noninvasive treatments are increasingly being used for the management of basal cell carcinoma (BCC), the predominant type of nonmelanoma skin cancer, making the development of noninvasive diagnostic technologies highly relevant for clinical practice. Laser-induced fluorescence (LIF) spectroscopy emerges as an attractive diagnostic technique for the diagnosis and demarcation of BCC due to its noninvasiveness, high sensitivity, real-time measurements, and user-friendly methodology. LIF relies on the principle of differential fluorescence emission between abnormal and normal skin tissues (ex vivo and in vivo) in response to excitation by a specific wavelength of light. Fluorescence originates either from endogenous fluorophores (autofluorescence) or from exogenously administered fluorophores (photosensitizers). The measured optical properties and fluorophore contributions of normal skin and BCC are significantly different from each other and correlate well with tissue histology. Photodynamic diagnosis (PDD) is based on the visualization of a fluorophore, with the ability to accumulate in tumor tissue, by the use of fluorescence imaging. PDD may be used for detecting subclinical disease, determining surgical margins, and following-up patients for residual tumor or BCC relapse. In this review, we will present the basic principles of LIF and discuss its uses for the diagnosis, management, and follow-up of BCC.

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“…As the precursor of heme, protoporphyrin IX can be endogenously synthesized via the metabolic pathway and preferentially accumulated in rapid proliferating cancer cells due to the decreased level of ferrochelatase and the increased activity of PBGD (porphobilinogen deaminase) of tumor cells [3,4]. On the one hand, the endogenous protoporphyrin IX (ALA-PpIX) indirectly generated by δ-Aminolevulinic acid (5-ALA) has been well investigated in photodynamic theraphy (PDT) [5,6]. On the other hand, previous study has reported the synergistic effect of ultrasound and exogenous protoporphyrin IX (PpIX) in sonodynamic therapy (SDT), in which PpIX was administrated to cells directly [7,8].…”

Section: Introductionmentioning

confidence: 99%

DNA Damage and Cell Cycle Arrest Induced by Protoporphyrin IX in Sarcoma 180 Cells

Wang

Zhang

et al. 2013

Cell Physiol Biochem

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Background: Porphyrin derivatives have been widely used in photodynamic therapy as effective sensitizers. Protoporphyrin IX (PpIX), a well-known hematoporphyrin derivative component, shows great potential to enhance light induced tumor cell damage. However, PpIX alone could also exert anti-tumor effects. The mechanisms underlying those direct effects are incompletely understood. This study thus investigated the putative mechanisms underlying the anti-tumor effects of PpIX on sarcoma 180 (S180) cells. Methods: S180 cells were treated with different concentrations of PpIX. Following the treatment, cell viability was evaluated by the 3-(4, 5- dimethylthiazol-2-yl)-2, 5-diphenyltetrazoliumbromide (MTT) assay; Disruption of mitochondrial membrane potential was measured by flow cytometry; The trans-location of apoptosis inducer factor (AIF) from mitochondria to nucleus was visualized by confocal laser scanning microscopy; DNA damage was detected by single cell gel electrophoresis; Cell cycle distribution was analyzed by DNA content with flow cytometry; Cell cycle associated proteins were detected by western blotting. Results: PpIX (≥ 1 µg/ml) significantly inhibited proliferation and reduced viability of S180 cells in a dose-dependent manner. PpIX rapidly and significantly triggered mitochondrial membrane depolarization, AIF (apoptosis inducer factor) translocation from mitochondria to nucleus and DNA damage, effects partially relieved by the specific inhibitor of MPTP (mitochondrial permeability transition pore). Furthermore, S phase arrest and upregulation of the related proteins of P53 and P21 were observed following 12 and 24 h PpIX exposure. Conclusion: PpIX could inhibit tumor cell proliferation by induction of DNA damage and cell cycle arrest in the S phase.

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Kinetic fluorescence studies of 5-aminolaevulinic acid-induced protoporphyrin IX accumulation in basal cell carcinomas

Cited by 75 publications

References 32 publications

Preferential accumulation of 5-aminolevulinic acid-induced protoporphyrin IX in breast cancer: a comprehensive study on six breast cell lines with varying phenotypes

Preferential accumulation of 5-aminolevulinic acid-induced protoporphyrin IX in breast cancer: a comprehensive study on six breast cell lines with varying phenotypes

Laser-induced fluorescence made simple: implications for the diagnosis and follow-up monitoring of basal cell carcinoma

DNA Damage and Cell Cycle Arrest Induced by Protoporphyrin IX in Sarcoma 180 Cells

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