- Visualizing protoporphyrin IX formation in the dura tail of meningiomas by mass spectrometry imaging. [Journal Article]
- ANActa Neurochir (Wien) 2018 Feb 15
- CONCLUSIONS: MALDI-MS/MS visualized a selective accumulation of PpIX within the tumor tissue including the dura tail. Thus, absence of fluorescence in the dura tail as visualized by the operating microscope is not caused by the lack of PpIX formation.
- H2O2mediates ALA-induced glutathione and ascorbate accumulation in the perception and resistance to oxidative stress in Solanum lycopersicum at low temperatures. [Journal Article]
- BPBMC Plant Biol 2018 Feb 15; 18(1):34
- CONCLUSIONS: Appropriate concentrations of ALA alleviated the low temperature-induced oxidative stress in tomato plants via an antioxidant system. The most effective concentration was 25 mg·L- 1. The results showed that H2O2induced by exogenous ALA under normal conditions is crucial and may be the initial step for perception and signaling transmission, which then improves the ratio of GSH and AsA. GSH and AsA may then interact with H2O2signaling, resulting in enhanced antioxidant capacity in tomato plants at low temperatures.
- Intraoperative Photodynamic Diagnosis Using Talaporfin Sodium Simultaneously Applied for Photodynamic Therapy against Malignant Glioma: A Prospective Clinical Study. [Journal Article]
- FNFront Neurol 2018; 9:24
- CONCLUSIONS: Intraoperative simultaneous PDD and PDT with TS can be performed for patients with malignant glioma. The blue excitation light that is used for 5-aminolevulinic acid PDD can be used for our technique (TS-PDD). The strong fluorescence from pathologically malignant tissues may be due at least in part to the involvement of microvascular structures.
- Role of Endogenous Nitric Oxide in Hyperaggressiveness of Tumor Cells that Survive a Photodynamic Therapy Challenge. [Journal Article]
- CRCrit Rev Oncog 2016; 21(5-6):353-363
- Many malignant tumors exploit nitric oxide (NO) for a survival, growth, and migration/invasion advantage, and also to withstand the cytotoxic effects of chemo- and radiotherapies. Endogenous NO has a...
Many malignant tumors exploit nitric oxide (NO) for a survival, growth, and migration/invasion advantage, and also to withstand the cytotoxic effects of chemo- and radiotherapies. Endogenous NO has also been shown to antagonize photodynamic therapy (PDT), a unique minimally invasive modality involving a photosensitizing (PS) agent, PS-exciting light in the visible- to near-infrared range, and molecular oxygen. The anti-PDT effects of NO were discovered about 20 years ago, but the underlying mechanisms are still not fully understood. More recent studies in the author's laboratory using breast, prostate, and brain cancer cell lines have shown that inducible NO synthase (iNOS/NOS2) is dramatically upregulated after a PDT challenge using 5-aminolevulinic acid (ALA-) -induced protoporphyrin IX as the PS. The parallel increase in NO resulted not only in a greater resistance to cell killing but also in a striking increase in the growth and migration/invasion rate of surviving cells. These in vitro findings and their recent recapitulation at the in vivo level are discussed in this article, along with how iNOS/NO's negative effects on PDT can be attenuated by the use of select iNOS inhibitors as PDT adjuvants.
- Remodeling of dermal collagen in photoaged skin using low-dose 5-aminolevulinic acid photodynamic therapy occurs via the TGF-β pathway. [Journal Article]
- JBJ Biophotonics 2018 Feb 12
- 5-Aminolevulinic acid photodynamic therapy (ALA-PDT) is known to be effective in the treatment of photoaged skin. However, the molecular mechanisms still remain elusive. Protoporphyrin IX (PpIX) fluo...
5-Aminolevulinic acid photodynamic therapy (ALA-PDT) is known to be effective in the treatment of photoaged skin. However, the molecular mechanisms still remain elusive. Protoporphyrin IX (PpIX) fluorescence is primarily located in the epidermis while ALA-PDT affects the dermal collagen, presumably by an indirect mechanism. This study aimed to investigate the molecular communication in low-dose ALA-PDT occurring between epidermal keratinocytes and dermal fibroblasts. Western blotting and enzyme-linked immunosorbent assays were performed to evaluate collagen expression and transforming growth factor-β (TGF-β) signaling in human keratinocytes and dermal fibroblasts. The impact on fibroblast proliferation was assessed by morphology and proliferating cell nuclear antigen immunofluorescence. Skin biopsies from mice were used to analyze the histological changes in dermal collagen and PpIX distribution. When fibroblasts were co-cultured with keratinocytes treated with low-dose ALA-PDT, collagen synthesis and fibroblast proliferation were enhanced. Low-dose ALA-PDT stimulated TGF-β1 expression in keratinocytes. Fibroblasts co-cultured with low-dose ALA-PDT treated keratinocytes also showed activation of the TGF-β pathway. In vivo, PpIX fluorescence was densely distributed in photoaged mouse epidermis while collagen in the mouse dermis underwent remodeling. This study suggests that low-dose ALA-PDT can stimulate keratinocytes to release TGF-β1, activating the TGF-β pathway in dermal fibroblasts to remodel collagen in the dermis.
- The influence of different illumination parameters on protoporphyrin IX induced cell death in squamous cell carcinoma cells. [Journal Article]
- PPPhotodiagnosis Photodyn Ther 2018 Feb 07
- CONCLUSIONS: In both, A431 and SCC-13 cells, total light dose is a key factor for photodynamic efficacy. Additionally, our results hint towards a threshold concentration of PpIX upon which a drastic loss of viability occurs. Light fluence rate is not a limiting factor, which may allow for the clinical implementation of low fluence rate protocols for pain management.
- Verification of radiodynamic therapy by medical linear accelerator using a mouse melanoma tumor model. [Journal Article]
- SRSci Rep 2018 Feb 09; 8(1):2728
- Combined treatment with 5-aminolevulinic acid (5-ALA) and X-rays improves tumor suppression in vivo. This is because the accumulated protoporphyrin IX from 5-ALA enhances the generation of ROS by the...
Combined treatment with 5-aminolevulinic acid (5-ALA) and X-rays improves tumor suppression in vivo. This is because the accumulated protoporphyrin IX from 5-ALA enhances the generation of ROS by the X-ray irradiation. In the present study, a high-energy medical linear accelerator was used instead of a non-medical low energy X-ray irradiator, which had been previously used. Tumor-bearing mice implanted with B16-BL6 melanoma cells were treated with fractionated doses of irradiation (in total, 20 or 30 Gy), using two types of X-ray irradiator after 5-ALA administration. Suppression of tumor growth was enhanced with X-ray irradiation in combination with 5-ALA treatment compared with X-ray treatment alone, using both medical and non-medical X-ray irradiators. 5-ALA has been used clinically for photodynamic therapy. Thus, "radiodynamic therapy", using radiation from medical linacs as a physical driving force, rather than the light used in photodynamic therapy, may have potential clinical applications.
- Protoporphyrinogen oxidase is involved in the fluorescence intensity of 5-aminolevulinic acid-mediated laser-based photodynamic endoscopic diagnosis for early gastric cancer. [Journal Article]
- PPPhotodiagnosis Photodyn Ther 2018 Feb 06
- CONCLUSIONS: PPOX protein expression could be involved in the fluorescence intensity of LPDED in EGC, possibly reflecting histopathological features.
- With a Little Help from My Friends: The Role of Intraoperative Fluorescent Dyes in the Surgical Management of High-Grade Gliomas. [Review]
- BSBrain Sci 2018 Feb 07; 8(2)
- High-grade gliomas (HGGs) are the most frequent primary malignant brain tumors in adults, which lead to death within two years of diagnosis. Maximal safe resection of malignant gliomas as the first s...
High-grade gliomas (HGGs) are the most frequent primary malignant brain tumors in adults, which lead to death within two years of diagnosis. Maximal safe resection of malignant gliomas as the first step of multimodal therapy is an accepted goal in malignant glioma surgery. Gross total resection has an important role in improving overall survival (OS) and progression-free survival (PFS), but identification of tumor borders is particularly difficult in HGGS. For this reason, imaging adjuncts, such as 5-aminolevulinic acid (5-ALA) or fluorescein sodium (FS) have been proposed as superior strategies for better defining the limits of surgical resection for HGG. 5-aminolevulinic acid (5-ALA) is implicated as precursor in the synthetic pathway of heme group. Protoporphyrin IX (PpIX) is an intermediate compound of heme metabolism, which produces fluorescence when excited by appropriate light wavelength. Malignant glioma cells have the capacity to selectively synthesize or accumulate 5-ALA-derived porphyrins after exogenous administration of 5-ALA. Fluorescein sodium (FS), on the other hand, is a fluorescent substance that is not specific to tumor cells but actually it is a marker for compromised blood-brain barrier (BBB) areas. Its effectiveness is confirmed by multicenter phase-II trial (FLUOGLIO) but lack of randomized phase III trial data. We conducted an analytic review of the literature with the objective of identifying the usefulness of 5-ALA and FS in HGG surgery in adult patients.
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- Photodynamic Therapy Activated by Intense Pulsed Light in the Treatment of Nonmelanoma Skin Cancer. [Journal Article]
- BBiomedicines 2018 Feb 07; 6(1)
- Photodynamic therapy (PDT) with topical 5-aminolevulinic acid (ALA) or methyl aminolevulinate (MAL) has proven to be a highly effective conservative method for the treatment of actinic keratosis (AK)...
Photodynamic therapy (PDT) with topical 5-aminolevulinic acid (ALA) or methyl aminolevulinate (MAL) has proven to be a highly effective conservative method for the treatment of actinic keratosis (AK), Bowen's disease (BD), and superficial basal cell carcinoma (sBCC). PDT is traditionally performed in association with broad-spectrum continuous-wave light sources, such as red or blue light. Recently, intense pulsed light (IPL) devices have been investigated as an alternative light source for PDT in the treatment of nonmelanoma skin cancers (NMSC). We herein report our observational findings in a cohort of patients with a diagnosis of AK, sBCC, and BD that is treated with MAL-PDT using IPL, as well as we review published data on the use of IPL-PDT in NMSC.