Porphyrins as urinary biomarkers for bladder cancer after 5-aminolevulinic acid (ALA) administration: The potential of photodynamic screening for tumors

Inoue, Keiji; Ota, Urara; Ishizuka, Masahiro; Kawada, Chiaki; Fukuhara, Hideo; Shuin, Taro; Okura, Ichiro; Tanaka, Tohru; Ogura, Shun‐ichiro

doi:10.1016/j.pdpdt.2013.05.002

Cited by 27 publications

(23 citation statements)

References 11 publications

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“…found in blood and, more importantly, in urine. 16 All have overlapping spectral profiles, and hence the three components in decay times could be due to three different types of porphyrins.…”

Section: Discussionmentioning

confidence: 99%

Cervical cancer detection by time-resolved spectra of blood components

et al. 2014

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Abstract. Fluorescence spectral techniques are very sensitive, and hence they are gaining importance in cancer detection. The biomarkers indicative of cancer could be identified and quantified by spectral or time domain fluorescence spectroscopy. The results of an investigation of time-resolved spectra of cellular components of blood obtained from cervical cancer patients and normal controls are given. The cancer indicative biomarker in this paper is porphyrin; it has a fluorescence decay time of 60% more in samples of cancer patients than those of normal controls. Based on such measurements, a randomized set comprising samples from cancer patients and controls (N ¼ 27 in total) could be classified with sensitivity (92%) and specificity (86%).

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Section: Discussionmentioning

confidence: 99%

Cervical cancer detection by time-resolved spectra of blood components

et al. 2014

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“…On the other hands, there were no significant differences in CP concentrations between healthy and tumour‐bearing mice . Studies showed that administration of 5‐ALA to patients with bladder cancer induced urine UPI and CPI levels in patients with bladder cancer that were higher than those of healthy adults . It was also reported that an average peak PpIX plasma concentration of 742 µg L −1 (5.6 µM) was obtained 6.7 h after oral administration of 40 mg kg −1 5‐ALA HCl to human patients .…”

Section: Discussionmentioning

confidence: 78%

“…Inoue et al reported that following administration of 5‐ALA, urine UPI and CPI levels of patients with bladder cancer were strongly elevated and showed high sensitivity (100% each) and specificity (96.4 and 91.4% for UPI and CPI, respectively). This result suggests that urinary porphyrins levels determined after administration of 5‐ALA could function as tumour markers . In this study, while PpIX was not detected in the plasma of healthy dogs, its plasma levels were elevated in dogs with MGTs following 5‐ALA administration.…”

Section: Discussionmentioning

confidence: 99%

Photodynamic detection of canine mammary gland tumours after oral administration of 5‐aminolevulinic acid

Osaki

Yokoe

Ogura

et al. 2016

Vet Comparative Oncology

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5-Aminolevulinic acid (5-ALA) is widely used in photodynamic detection (PDD) and therapy. We evaluated the pharmacokinetics of 5-ALA-induced porphyrins and its effectiveness in PDD in dogs with mammary gland tumours (MGTs) following oral administration. Healthy dogs and those with MGTs (nine each) were orally administered 4 mg kg 5-ALA. Protoporphyrin IX (PpIX) was not detected in the plasma of healthy dogs but it peaked in dogs with MGT at 2 h after 5-ALA administration. In the PDD study, 16 dogs with MGT were orally administered 40 mg kg 5-ALA, and MGT but not normal tissue showed red fluorescence after 2-4 h. Photon counts were 6635-63 890 and 59-4011 (median, 19 943 and 919) for MGT and non-tumour tissues, respectively. Cell density strongly correlated with PpIX photon counts of MGT tissue of the dogs (R = 0.743, P = 0.0009). We suggest that 5-ALA-PDD might be an effective diagnostic tool for MGTs.

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“…Cells were incubated with 1 mM ALA under 5% CO 2 at 37 °C in normoxia (21% oxygen) or hypoxia (1% oxygen) in the dark for 24 h. High-performance liquid chromatography (HPLC) analysis was performed as previously described with some modifications1147. Cells were washed and lysed using 0.1 M NaOH, and lysates were extracted by addition of three volumes of DMF/2-propanol (100:1, v/v).…”

Section: Methodsmentioning

confidence: 99%

Dormant cancer cells accumulate high protoporphyrin IX levels and are sensitive to 5-aminolevulinic acid-based photodynamic therapy

Nakayama

Otsuka

Kobayashi

et al. 2016

Sci Rep

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Photodynamic therapy (PDT) and diagnosis (PDD) using 5-aminolevulinic acid (ALA) to drive the production of an intracellular photosensitizer, protoporphyrin IX (PpIX), are in common clinical use. However, the tendency to accumulate PpIX is not well understood. Patients with cancer can develop recurrent metastatic disease with latency periods. This pause can be explained by cancer dormancy. Here we created uniformly sized PC-3 prostate cancer spheroids using a 3D culture plate (EZSPHERE). We demonstrated that cancer cells exhibited dormancy in a cell density-dependent manner not only in spheroids but also in 2D culture. Dormant cancer cells accumulated high PpIX levels and were sensitive to ALA-PDT. In dormant cancer cells, transporter expressions of PEPT1, ALA importer, and ABCB6, an intermediate porphyrin transporter, were upregulated and that of ABCG2, a PpIX exporter, was downregulated. PpIX accumulation and ALA-PDT cytotoxicity were enhanced by G0/G1-phase arrestors in non-dormant cancer cells. Our results demonstrate that ALA-PDT would be an effective approach for dormant cancer cells and can be enhanced by combining with a cell-growth inhibitor.

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Porphyrins as urinary biomarkers for bladder cancer after 5-aminolevulinic acid (ALA) administration: The potential of photodynamic screening for tumors

Cited by 27 publications

References 11 publications

Cervical cancer detection by time-resolved spectra of blood components

Cervical cancer detection by time-resolved spectra of blood components

Photodynamic detection of canine mammary gland tumours after oral administration of 5‐aminolevulinic acid

Dormant cancer cells accumulate high protoporphyrin IX levels and are sensitive to 5-aminolevulinic acid-based photodynamic therapy

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