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 685,946 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Our recent study found that a new topical 5-aminolevulinic acid-mediated photodynamic therapy (ALA-PDT) protocol composed of multiple 3-min fractionated irradiations with a light emitting diode (LED) red light at 635 +/- 5 nm for a total of 1000 s (fluence rate: 100 mW/cm(2); light exposure dose: 100 J/cm(2)) after topical application of 20% ALA for 1.5 or 2 h can be used successfully for the treatment of oral verrucous hyperplasia. In this case report, we tested the efficacy of this new treatment protocol of ALA-PDT for an extraoral verrucous carcinoma (VC) lesion at the right mouth angle and an intraoral VC lesion at the right buccal mucosa of a 56-year-old male areca quid chewer and smoker. The extraoral tumor was cleared after six treatments of topical ALA-PDT and the intraoral tumor showed complete regression after 22 treatments of topical ALA-PDT. No recurrence of the VC lesion was found after a follow-up period of 6 months. We suggest that PDT using a topical application of 20% ALA followed by multiple 3-min fractionated irradiations with an LED red light is also an effective and successful treatment modality for VC.
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PMID:Successful treatment of an extensive verrucous carcinoma with topical 5-aminolevulinic acid-mediated photodynamic therapy. 1575 62

We have investigated the role of tissue oxygenation on light penetration into tissue at different wavelengths. As a field of application we have chosen aminolevulinic acid-photodynamic therapy (ALA-PDT). To calculate efficiency spectra of PDT on human skin one needs to know the excitation spectrum of the photosensitizer of interest and the relative fluence rate as a function of depth in the tissue. We measured the former and computed the latter with an accurate radiative transfer algorithm. In this way we determined the efficiency spectra as functions of depth for different types of basal cell carcinomas (BCC). Our results suggest that ALA-PDT works best for nodular BCC at a wavelength of 630 nm, whereas it works best for pigmented superficial BCC at a wavelength of 390 nm. At 630 nm the light penetration into a tumor depends strongly on the oxygenation of the blood. Below a 2 mm thick, well-oxygenated, nodular BCC, we find the efficiency to be an order of magnitude larger than below a poorly oxygenated tumor. At 390 nm, the light penetration into a tumor does not depend on the oxygenation of the blood.
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PMID:Choice of optimal wavelength for PDT: the significance of oxygen depletion. 1593 93

We report a case of a 73-year-old man with nevoid basal cell carcinoma syndrome who was referred to us with multiple basal cell carcinomas on his face and chest. The patient underwent photodynamic therapy utilizing a 1-hour incubation of Levulan Kerastick delta-aminolevulinic acid 20% topical solution applied to the full face and illumination with a BLU-U blue light source (10 J/cm2) every 2 to 3 months for a total of 4 treatments. This treatment strategy resulted in multiple benefits, including reducing the number and size of his existing basal cell carcinomas, improving the appearance of previous surgical scars, and decreasing the rate of tumor development.
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PMID:Broad area photodynamic therapy for treatment of multiple basal cell carcinomas in a patient with nevoid basal cell carcinoma syndrome. 1648 73

Especially in the public, vitamin C is considered supportive for the treatment of cancer and supplementation is common. However, the underlying mechanism that most chemotherapeutic agents, ionizing radiation, and photodynamic therapy exert on tumor cell kill is an increased production of reactive oxygen species (ROS) leading to irreversible tissue injury. Therefore, antioxidants like ascorbic acid (AA) may prevent cancer cells of cellular free radical damage and may therefore be contraindicated in patients undergoing tumor treatment. We report on the effects of AA on markers of oxidative stress and apoptosis in rat DS-sarcoma cells on 5-aminolevulinic acid-based photodynamic therapy (ALA-PDT). AA dose-dependently protected cancer cells against lipid and protein oxidation caused by ALA-PDT treatment. By real-time RT-PCR analysis an impressive increase of FasL (124-fold) and TNF-alpha (121-fold) mRNA was detected after PDT treatment. In addition, a decrease in mitochondrial transmembrane potential followed by the mitochondrial release of apoptosis-inducing factor (AIF) was observed. All these early signs of apoptosis were significantly reduced by AA, resulting in a 2.1-fold increased cell survival rate on ALA-PDT treatment. In conclusion, AA functions as a potent antioxidant, protecting mitochondria and other cell structures of oxidative cell injury induced by ALA-PDT and may therefore be contraindicated in patients undergoing tumor treatment.
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PMID:Ascorbic acid suppresses cell death in rat DS-sarcoma cancer cells induced by 5-aminolevulinic acid-based photodynamic therapy. 1652 Feb 35

The introduction of lipophilic derivatives of the naturally occurring heme precursor 5-aminolevulinic acid (5-ALA) into photomedicine has led to a true revival of this research area. 5-ALA-mediated photodynamic therapy (PDT) and fluorescence photodetection (FD) of neoplastic disease is probably one of the most selective cancer treatments currently known in oncology. To date, this method has been assessed experimentally for the treatment of various medical indications. However, the limited local bioavailability of 5-ALA has widely prevented its use in daily clinical practice. Although researchers were already aware of this drawback early during the development of 5-ALA-mediated PDT, only recently have well-established concepts in pharmaceutical science been adapted to investigate ways to overcome this drawback. Recently, two derivatives of 5-ALA, methylaminolevulinate (MAL) and hexylaminolevulinate (HAL), gained marketing authorization from the regulatory offices in Europe and Australia. MAL is marketed under the trade name Metvix for the treatment of actinic keratosis and difficult-to-treat basal cell carcinoma. HAL has recently been launched under the trade name Hexvix to improve the detection of superficial bladder cancer in Europe. This review will first present the fundamental concepts underlying the use of 5-ALA derivatives in PDT and FD from a chemical, biochemical and pharmaceutical point of view. Experimental evidences from preclinical data on the improvements and limits observed with 5-ALA derivatives will then be introduced. The state-of-the-art from clinical studies with 5-ALA esters will be discussed, with special emphasis placed on the process that led to the development of MAL in dermatology and to HAL in urology. Finally, we will discuss promising medical fields in which use of 5-ALA derivatives might potentially lead to further use of this methodology in photomedicine.
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PMID:5-Aminolevulinic acid derivatives in photomedicine: Characteristics, application and perspectives. 1654 12

Photodynamic therapy (PDT) typically involves systemic or topical administration of a tumor-localizing photosensitizer or prodrug and its subsequent activation by visible light. This results primarily in singlet oxygen-induced photodamage to the tumor. 5-Aminolevulinic acid (ALA) and its derivatives have recently been widely used for PDT due to their selective induction in tumor of endogenous protoporphyrin IX (PpIX), a potent photosensitizer. Although ALA-PDT has achieved successful results in the treatment of several clinical oncological and nononcological diseases, the mechanisms of this modality are still not fully elucidated. In the present study, the human colon carcinoma cell line 320DM was treated in vitro with PDT using hexaminolevulinate (HAL), a hexylester of ALA known to be 50 to 100 times more efficient at producing PpIX formation than ALA itself. PpIX production increased with increasing HAL concentrations in the cells and phototoxicity of the cells was enhanced with increasing light (450 nm) doses. HAL-PDT induced apoptotic cell death, as measured by nuclear staining of Hoechst 33342 for fluorescence microscopy, DNA electrophoresis and TdT staining for flow cytometry. PDT with 5 muM of HAL and a light dose of 640 mJ/cm2 produced a 75% apoptotic cell population 40 hr after the treatment. Furthermore, the loss of mitochondrial membrane potential coincident with the release of cytochrome c from the mitochondria into the cytosol led to a rapid activation of caspase-9 and caspase-3 (an executioner), indicating that the selective damage to the mitochondria by HAL-PDT can induce a cytochrome-c-mediated apoptotic response in the 320DM cells.
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PMID:Induction of apoptosis by hexaminolevulinate-mediated photodynamic therapy in human colon carcinoma cell line 320DM. 1656 15

5-Aminolevulinic acid (ALA) is now being increasingly used in photodynamic therapy (PDT) and photodiagnosis (PDD) of lesions of the oral cavity, esophagus, and female genital tract. Clearly, topically applied creams and solutions are not the most suitable drug delivery systems for such moist and irregularly shaped areas, where shear forces may be high. As a result, such areas of the body are currently relatively inaccessible to efficient topical delivery of ALA. The use of a bioadhesive patch for topical delivery of ALA to the lower female genital tract and now, for the first time, to the human lip, is described. Use of the patch, containing 38 mg ALA cm-2, allowed successful PDT of vulval intraepithelial neoplasia lesions and induced protoporphyrin IX production in Herpes simplex lesions of the lip.
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PMID:Facilitated delivery of ALA to inaccessible regions via bioadhesive patch systems. 1656 30

5-Aminolevulinic acid (5-ALA) is a well characterized precursor in the synthesis of various endogenous porphyrins used in photodynamic therapy (PDT). It is most often administered topically into a tumor which is then irradiated with visible light at established wavelength to sensitize porphyrins accumulated therein. Our main aim in the present study was to increase the penetration of 5-ALA through the altered skin by application of 3% azone (1-dodecyl-azepan-2-one) before the application of 20% 5-ALA in patients with plantar warts: mosaic warts (MW) and myrmecia (MY). We also used 20% 5-ALA only to treat warts in other patients. We compared the therapeutic and cosmetic effects of the two treatment modalities. The lesions treated with modification of 5-ALA-PDT by pretreatment with azone responded with better effectiveness. In 18 patients subjected to 5-ALA-PDT plus 3% azone, we observed 66.7% complete response of MW and 100% of MY following PDT repeated two or three times; whereas in other 18 patients treated with 5-ALA-PDT alone, we observed only 37.5% complete response of MW and 70% of MY. These results provide evidence that the pretreatment with azone should be considered as the step that enhances 5-ALA penetration in tissues and thus increases the effectiveness of applied PDT.
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PMID:Pretreatment of plantar warts with azone enhances the effect of 5-aminolevulinic acid photodynamic therapy. 1656 31

The role of photodynamic therapy (PDT) in the treatment of in situ neoplasias and tumors of the skin is steadily increasing. An intratumoral enriched photosensitizer and its activation by light are the principles of photodynamic action. Aminolevulinic acid (ALA) has been shown to be the drug with most experimental and clinical use in the past. The highest efficacy with most selectivity in topical PDT is postulated for methyl aminolevulinate or methyl aminooxopenoat (MAL, MAOP, Metvix). For solar keratoses, topical PDT using MAL is already considered to be the treatment of choice. Epithelial skin tumors such as basal cell carcinomas also respond very well, however, a debulking procedure of the exophytic tumor tissue is an absolute prerequisite to a successful cure. In addition to functioning as a novel therapeutic tool, photodynamic sensitization of skin cancer cells is increasingly used for fluorescence diagnosis (FD) (also known as photodynamic diagnosis or PDD). The fluorescence of induced porphyrins is effective in detecting and delineating neoplastic skin areas. Future approaches of FD and PDT are nontumoral applications, especially psoriasis, viral-induced diseases, or acne vulgaris. Topical PDT is well tolerated and leads to excellent aesthetic results with only minor side effects.
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PMID:Fluorescence diagnosis and photodynamic therapy in dermatology from experimental state to clinic standard methods. 1656 33

Photodynamic therapy (PDT) is an established treatment for the ablation of dysplastic Barrett's epithelium and early esophageal carcinoma, but no data have been published on curative 5-aminolevulinic acid (5-ALA)-PDT for long-segment early esophageal cancer with infiltration of the upper sphincter. We describe successful curative treatment of an unusual early long-segment squamous cell carcinoma (uT1a,N0) of the proximal esophagus (18 - 28 cm aborally), with three sessions of 5-ALA-PDT. Endoscopic and endosonographic follow-up macroscopically showed a complete remission of the tumor, proven by biopsy showing total histological ablation. After a follow-up period of 23 months, there has been no indication of tumor recurrence. Early superficial (< 3 mm) squamous cell carcinomas of the esophagus can be ablated completely by 5-ALA-PDT. However, long-term follow-up is required in order to prove the effectiveness of endoscopic ablation therapy for early esophageal cancer.
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PMID:Long-Segment early squamous cell carcinoma of the proximal esophagus: curative treatment and long-term follow-up after 5-aminolevulinic acid (5-ALA)-photodynamic therapy. 1680 73


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