- The efficacy and tolerability of 5-aminolevulinic acid 5% thermosetting gel photodynamic therapy (PDT) in the treatment of mild-to-moderate acne vulgaris. A two-center, prospective assessor-blinded, proof-of-concept study. [Journal Article]
- JCJ Cosmet Dermatol 2018 May 22
- CONCLUSIONS: This proof-of-concept study supports the efficacy of 5% ALA thermosetting gel red-light PDT in inflammatory acne of the face with a relevant clinical improvement of inflammatory lesions with a very good tolerability profile. Clinical improvement was maintained in the medium term (Trial Registration Number: ISRCTN66066651).
- [Progression of basic research, clinical application of photodynamic therapy and fluorescence-guided surgery in glioma treatment]. [Journal Article]
- ZNZhong Nan Da Xue Xue Bao Yi Xue Ban 2018 Apr 28; 43(4):360-367
- The prognosis of glioma remains poor because of the infiltrative nature and the high local relapse rate. The current goals for patients with gliomas is maximal safe resection and adjuvant therapy. Tu...
The prognosis of glioma remains poor because of the infiltrative nature and the high local relapse rate. The current goals for patients with gliomas is maximal safe resection and adjuvant therapy. Tumor-specific photosensitizer, such as hematoporphyrin derivative (HpD) 5-aminolevulinic acid (5-ALA), can be selective up-taken and accumulated in tumor tissue. Light with appropriate wavelength can penetrate tumor tissue and excite the photosensitizer. The excited photosensitizer within glioma cells permits fluorescence visualization of tumor tissue during surgery and has been introduced in treatment of glioma as fluorescence-guided surgery (FGS). On the other hand, the toxicity of singlet oxygen generated by the excited photosensitizer has been used as photodynamic therapy (PDT) in selective destruction of the tumor. Some reports demonstrated the usefulness of adding PDT as an intraoperative adjuvant therapy, but the complexity associated with its implementation and the introduction of TMZ prevented PDT from becoming a routine therapy. However, FGS using 5-ALA in patients with malignant brain tumors has surfaced globally and may become a useful tool in increasing the extent of resection in gliomas.
- Successful Sequential Treatment with Itraconazole and ALA-PDT for Cutaneous Granuloma by Candida albicans: A Case Report and Literature Review. [Journal Article]
- MMycopathologia 2018 May 16
- Photodynamic therapy (PDT) is a process that combines a photosensitizing drug and light and promotes phototoxic responses in target cells, mainly via oxidative damage. Antifungal photodynamic therapy...
Photodynamic therapy (PDT) is a process that combines a photosensitizing drug and light and promotes phototoxic responses in target cells, mainly via oxidative damage. Antifungal photodynamic therapy has been successfully employed against Candida species, dermatophytes, and deep mycoses. We present a case of a cutaneous granuloma caused by C. albicans treated with 5-aminolevulinic acid (ALA)-PDT. A 64-year-old man presented with two plaques on his right hand and wrist for 2 years. The diagnosis was made based on histopathology, mycology, and molecular identification of paraffin-embedded tissues. The patient was treated with itraconazole for 1 month and two sessions of ALA-PDT. After 2 months of follow-up, the patient was cured and has not experienced any recurrence to date. ALA-PDT was well tolerated in this patient with little pain. In general, application of PDT in mycoses is safe and effective in most cases. ALA-PDT is a good choice for inactivation of C. albicans.
- Enhanced resection of primary high-grade gliomas using a combination of intraoperative magnetic resonance imaging and intraoperative fluorescence (5-aminolevulinic acid): A single-centre experience. [Journal Article]
- NINeurol India 2018 May-Jun; 66(3):747-752
- CONCLUSIONS: The use of iMRI as well as fluorescence-guidance are appropriate methods to improve the extent of resection in surgery of contrast-enhancing gliomas. Best results can be achieved by the complementary use of both modalities.
- 5-Aminolevulinic Acid-Mediated Sonodynamic Therapy Alleviates Atherosclerosis via Enhancing Efferocytosis and Facilitating a Shift in the Th1/Th2 Balance Toward Th2 Polarization. [Journal Article]
- CPCell Physiol Biochem 2018 May 09; 47(1):83-96
- CONCLUSIONS: ALA-SDT alleviates AS by enhancing cytotoxic effects on Th cells, subsequently stimulating efferocytosis and facilitating a shift in the Th1/Th2 balance toward Th2 cells, a discovery that might help elucidate the mechanism underlying SDT as a potential treatment to prevent atherothrombotic events.
- 5-ALA fluorescence and laser Doppler flowmetry for guidance in a stereotactic brain tumor biopsy. [Journal Article]
- BOBiomed Opt Express 2018 May 01; 9(5):2284-2296
- A fiber optic probe was developed for guidance during stereotactic brain biopsy procedures to target tumor tissue and reduce the risk of hemorrhage. The probe was connected to a setup for the measure...
A fiber optic probe was developed for guidance during stereotactic brain biopsy procedures to target tumor tissue and reduce the risk of hemorrhage. The probe was connected to a setup for the measurement of 5-aminolevulinic acid (5-ALA) induced fluorescence and microvascular blood flow. Along three stereotactic trajectories, fluorescence (n = 109) and laser Doppler flowmetry (LDF) (n = 144) measurements were done in millimeter increments. The recorded signals were compared to histopathology and radiology images. The median ratio of protoporphyrin IX (PpIX) fluorescence and autofluorescence (AF) in the tumor was considerably higher than the marginal zone (17.3 vs 0.9). The blood flow showed two high spots (3%) in total. The proposed setup allows simultaneous and real-time detection of tumor tissue and microvascular blood flow for tracking the vessels.
- Oral administration of 5-aminolevulinic acid induces heme oxygenase-1 expression in peripheral blood mononuclear cells of healthy human subjects in combination with ferrous iron. [Journal Article]
- EJEur J Pharmacol 2018 May 10
- Heme oxygenase-1 (HO-1) is a major anti-inflammatory enzyme and a key regulator that induces immune tolerance through affecting the differentiation of dendritic cells. The aim of this study is to det...
Heme oxygenase-1 (HO-1) is a major anti-inflammatory enzyme and a key regulator that induces immune tolerance through affecting the differentiation of dendritic cells. The aim of this study is to determine whether the combination of 5-aminolevulinic acid (ALA) and iron induces HO-1 expression in healthy human peripheral blood mononuclear cells (PBMC). The study was an open labeled, non-randomized, non-placebo-controlled trial using healthy male adults and consisted of three parts. Study A aimed to find the peak HO-1 expression at 0, 1, 2, 3, 4, 6, 8, 12, 16, and 24h after administration. Study B aimed to examine HO-1 dose dependency at 150, 300, and 600mg of ALA and the need for iron supplementation. Study C aimed to investigate HO-1 changes during a three-day, repetitive administration of ALA and iron. The combination of ALA 600mg and sodium ferrous citrate (SFC) 942mg upregulated HO-1 in PBMC at 8h after administration while sole administration of ALA or SFC was unable to induce HO-1. HO-1 in blood myeloid and plasmacytoid dendritic cells was also upregulated with ALA+SFC. Clear dose dependency of ALA+SFC was not detected, and a slight tendency towards a cumulative effect of HO-1 after three-day, repetitive administration was observed. ALA, which is already approved for use in several countries as a diagnosis agent for cancer, has the potential to become a novel therapeutic drug for diseases stemming from unwanted immune response such as autoimmune diseases and the rejection response following organ transplantation.
- Daylight Photodynamic Therapy for Actinic Keratoses. [Review]
- AJAm J Clin Dermatol 2018 May 11
- Topical photodynamic therapy (PDT) using daylight is effective in the treatment of actinic keratoses (AKs), offering the potential for treatment of large fields such as full face and balding scalp, b...
Topical photodynamic therapy (PDT) using daylight is effective in the treatment of actinic keratoses (AKs), offering the potential for treatment of large fields such as full face and balding scalp, but with minimal therapy-associated pain. Comparison with conventional PDT indicates similar efficacy for thin and moderate-thickness AKs, but with significantly less discomfort/pain, driving a patient preference for daylight-mediated PDT (DL-PDT) compared with conventional PDT using high-intensity office/hospital-based light sources. Treatment protocol involves the application of a photosensitizing agent without occlusion and subsequent exposure to ambient daylight within 30 min, with patients exposed to daylight for 1.5-2.0 h. Pivotal randomized controlled trials in Europe and Australia have confirmed the efficacy of methyl aminolevulinic acid (MAL) DL-PDT in comparison with conventional MAL-PDT for mild and moderate-thickness lesions on the face and scalp. Initial clearance rates of 70-89% are reported. DL-PDT using a nanoemulsion aminolevulinic acid (ALA) has recently been shown to be at least as effective as MAL DL-PDT in treating mild and moderate-thickness AKs. DL-PDT may offer a better-tolerated method for treating patients with extensive AK disease. There is emerging literature on the potential for field PDT to reduce the number of new AKs developing, potentially preventing/slowing skin cancer development. Conventional PDT remains established as a therapy for Bowen's disease (squamous cell carcinoma in situ), superficial and certain thin basal cell carcinomas (BCCs), and AKs. The evidence for the use of DL-PDT beyond AK is limited, although has been reported in actinic cheilitis, superficial BCC, and acne and cutaneous leishmaniasis. There is emerging interest in combination therapy for AK, using one or more field therapies such as DL-PDT as an option to complement with localized treatment for residual lesions. We review current recommendations and consider the appropriate place for DL-PDT in our treatment armamentarium.
- Potential involvement of the 18 kDa translocator protein and reactive oxygen species in apoptosis of THP-1 macrophages induced by sonodynamic therapy. [Journal Article]
- PlosPLoS One 2018; 13(5):e0196541
- Sonodynamic therapy (SDT) with exogenous protoporphyrin IX (PpIX) or endogenous PpIX derived from 5-aminolevulinic acid (ALA) has been carried out to produce apoptotic effects on macrophages, indicat...
Sonodynamic therapy (SDT) with exogenous protoporphyrin IX (PpIX) or endogenous PpIX derived from 5-aminolevulinic acid (ALA) has been carried out to produce apoptotic effects on macrophages, indicating a potential treatment methodology for atherosclerosis. Our previous studies have found that mitochondria damage by reactive oxygen species (ROS) plays a major role in the SDT-induced apoptosis. This study aimed at investigating the potential involvement of the mitochondrial 18 kDa translocator protein (TSPO) and ROS in the pro-apoptotic effects of SDT on THP-1 macrophages. THP-1 macrophages were divided into control and SDT groups, and went through pretreatment of the specific TSPO ligand PK11195 and ROS scavengers N-Acetyl Cysteine (NAC), then compared with groups without pretreatment. Application of PK11195 reduced intracellular accumulation of endogenous PpIX. PK11195 and NAC reduced the generation of intracellular ROS and oxidation of cardiolipin induced by SDT, respectively. PK11195 and NAC also reduced SDT-induced mitochondrial membrane potential (ΔΨm) loss, the translocation of cytochrome c and cell apoptosis. PpIX accumulation, ROS generation and cell apoptosis were also attenuated by siTSPO. Our findings indicate the pivotal role of TSPO and ROS in SDT-induced cardiolipin oxidation, ΔΨm collapse, cytochrome c translocation and apoptosis in THP-1 macrophages.
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- Pathway engineering in Corynebacterium glutamicum S9114 for 5-aminolevulinic acid production. [Journal Article]
- 3B3 Biotech 2018; 8(5):247
- 5-Aminolevulinic acid (ALA) is a non-protein amino acid with a significant potential for cancer treatment and plant stress resistance. Microbial fermentation has gradually replaced the traditional ch...
5-Aminolevulinic acid (ALA) is a non-protein amino acid with a significant potential for cancer treatment and plant stress resistance. Microbial fermentation has gradually replaced the traditional chemical-based method for ALA production, thus increasing the need for high-ALA-producing strains. In this study, we engineered the glutamate producing strain, Corynebacterium glutamicum S9114, for ALA production. To efficiently convert l-glutamate to ALA, hemA and hemL from Salmonella typhimurium and Escherichia coli were tandemly overexpressed. In addition, ncgl1221 encoding a glutamate transporter was deleted to block glutamate secretion and thus improve ALA production. Furthermore, the intrinsic ribosome-binding site (RBS) of hemB was replaced by a relatively weak RBS to reduce the conversion of ALA to porphyrin. Transcriptional and fermentation data confirmed that inactivation of lysE and putP reduced the conversion of glutamate to arginine and proline, which also contribute to ALA production. The final SA14 strain produced 895 mg/L concentration of ALA after 72 h incubation in a shake flask. This amount was 58-fold higher than that obtained by the parent strain C. glutamicum S9114. The results demonstrate the potential of C. glutamicum S9114 for efficient ALA production and provide new targets for the development of ALA-producing strains.