Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0025202 (melanoma)
 69,561 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The application of PDT in dermatology has been limited by technical problems, lack of standardized treatment parameters and controlled clinical trials, and cutaneous photosensitivity. PDT requires specially trained personnel and relies on devices that are expensive and difficult to maintain. In North America, PDT is currently performed at only a few centers on an investigational basis. Although a great deal of anecdotal clinical information is available on PDT for treating non-melanoma skin cancer, controlled trials are still needed in order to compare PDT with the highly effective methods already available. PDT may also be useful for a variety of nononcologic dermatoses. New photosensitizers such as BPD-MA, NPe6, and ALA offer the promise of causing significantly less prolonged photosensitivity than the currently available agents; combined with well-designed clinical studies, this will undoubtedly facilitate the acceptance of PDT into standard dermatologic practice.
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PMID:Photodynamic therapy in dermatology: recent developments. 843 4

Chromosome band 9p21 is a frequent target of homozygous deletion in many tumor types. Putative tumor suppressor genes, CDKN2A (p16), p14(ARF) and CDKN2B (p15), were localized to 9p21. However, there have been reports that suggest that there may be other genes targeted for inactivation in the region. We have developed a method to search for transcribed sequences within large genomic regions. We tested our approach in a 100-kilobase region on 9p21, which is 40 kilobases telomeric to CDKN2A. The method, termed expressed sequence selection (ESS), resulted in the isolation of genomic fragments known to be from 9q21 that are homologous to transcribed sequences. One fragment was used to obtain a 1.2 kilobase cDNA. The sequence of the 5' half of the cDNA was almost identical to exons 3-5 of the MTAP gene, which maps to chromosome band 9p21. The 3' portion of the cDNA had sequence homology to the ALA gene, which maps to chromosome arm 9q. Using Northern blot analysis, the 1.2 Kb cDNA identified several widely expressed transcripts ranging from 1 Kb to 8.5 Kb and displayed a complex pattern of alternative splicing in which certain exons of the 1.2 Kb cDNA are excluded from some of the splice products. Using cancer tissue Northern blots, we could show that all of the transcripts are absent from a leukemia cell line and a lung cancer cell line (K562, A549) with homozygous, genomic deletions within chromosome band 9p21. In addition, the 7 Kb transcript is also absent from two additional tumor cell lines (Molt4, a leukemia derived cell line, and in G361, a melanoma derived cell line) with homozygous deletions. Further investigation will determine whether the difference in the expression pattern between the 7 Kb transcript compared with the other sized transcripts could be due to specific targeting for alteration in certain tumor types.
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PMID:Identification of a 1.2 Kb cDNA fragment from a region on 9p21 commonly deleted in multiple tumor types. 1156 37

The purpose of this study was to estimate the efficacy of an endogenous sensitizer (delta-aminolevulinic acid (or ALA) induced protoporphyrin IX (or PpIX)) and an exogenous sensitizer (meta(tetrahydroxyphenyl)chlorin or m-THPC) on two different cell lines, rat colon adenocarcinoma PROb cells and murine melanoma B16A45 (B16) cells, in apoptosis production. After sensitizer incubation, cells were irradiated with an argon dye laser. LD(50) with m-THPC was 2.8 microg/ml and 4.7 microg/ml under irradiation of 25 J/cm(2) respectively for PROb and B16 cells. With ALA, LD(50) was 150 microg/ml and 175 microg/ml under 25 J/cm(2) respectively for PROb and B16 cells. Apoptosis induction by m-THPC or ALA-PDT was detected by DNA gel electrophoresis and quantified using an ELISA assay 24 h after PDT. The maximal apoptosis enrichment factor (MAEF) was reached for 6 microg/ml m-THPC at 10 J/cm(2) for PROb and B16 cells and for 50 microg/ml ALA at 25 J/cm(2) for PROb or B16 cells. Both m-THPC and PpIX are efficient photosensitizers and apoptosis inducers. However, MAEF is obtained by sensitizer or laser doses inducing very different phototoxic effects: MAEF was obtained after m-THPC-PDT with LD(78) for PROb cells and LD(30) for B16 cells and after ALA-PDT with LD(22) for PROb cells and LD(18) for B16 cells. However the overall m-THPC/PDT apoptotic induction (under the curve surface analysis) was not different whatever the cell line for 10 and 25 J/cm(2). On the contrary, ALA-PpIX/PDT apoptotic induction was twice for 25 J/cm(2) as compared to 50 J/cm(2) (p < 0.01) for both the PROb and B16 cells. These results indicate that the apoptosis rate in PDT cell killing varies considerably according to cell type and sensitizer.
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PMID:PDT effects of m-THPC and ALA, phototoxicity and apoptosis. 1199 66

No fluorescence of protoporphyrin IX (PpIX) was measured using a fiber optic probe in pigmented B16F10 melanoma in mice after topical application of 5-aminolevulinic acid methylester (ALA-Me). However, chemical extraction of tissues excised from mice after intratumoral administration of ALA-Me or its parent compound ALA revealed that this tumor had the capability to produce PpIX. Small amounts of endogenous porphyrins, mainly PpIX, were found in the melanoma not treated with these drugs. Topical application of ALA-Me followed by exposure with laser light (633nm) delayed the growth of the tumors slightly. Light alone also had a significant effect on the tumor growth.
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PMID:Photosensitizing effect of protoporphyrin IX in pigmented melanoma of mice. 1227 Jan 16

The use of 5-aminolevulinic acid (5-ALA) ester derivatives as precursors of endogenous protoporphyrin IX (PpIX) has been proposed as a good strategy for improved drug diffusion across biological membranes. In the present work, the 5-ALA ester derivatives hexyl-ALA (h-ALA), octyl-ALA (o-ALA), and decyl-ALA (d-ALA) were synthesized, and their efficacy to induce endogenous PpIX was explored in a murine melanoma cell line (B-16) as compared with that of 5-ALA. The maximum level of PpIX induced in cells treated with 5-ALA, h-ALA, o-ALA, and d-ALA was reached at optimal concentrations of 0.3, 0.075, 0.1, and 0.075 mM, respectively. The derivatives h-ALA and o-ALA appear as the most efficient PpIX precursors in this cell line, since a higher or similar PpIX production could be achieved with a fourfold and threefold lower dose of these precursors compared with 5-ALA. The phototoxicity effect of h-ALA and o-ALA ester derivatives showed the same phototoxicity behavior detected for 5-ALA but at much lower drug doses. Our study suggests that h-ALA and o-ALA esters improve intracellular PpIX formation in B-16 cells at reduced concentrations. This should enable clinical applications at lower precursor doses with reduced effective costs.
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PMID:5-aminolevulinic acid ester-induced protoporphyrin IX in a murine melanoma cell line. 1534 Aug 63

Photodynamic therapy (PDT) is widely used to treat preneoplastic skin lesions and non-melanoma skin tumours. Studies analyzing the effects of PDT on malignant melanoma have yielded conflicting results. On the one hand, melanoma cell lines in culture as well as cell lines transplanted into experimental animals were sensitive to PDT. On the other hand, spontaneous melanomas of human patients responded poorly to most PDT regimens tested so far. Here, we analyzed effects of 5-aminolaevulinic acid (5-ALA)-based PDT on melanoma cell lines and on experimental melanomas. To mimic the clinical situation as closely as possible, metallothionein-I/ret (MT-ret) mice, a transgenic model of skin melanoma development, were used. Optimal doses of 5-ALA as well as energy doses and power densities were determined in vitro using a cell line (Mel25) established by us from a melanoma of an MT-ret transgenic mouse as well as commercially available human and mouse melanoma cell lines. Treatment with light irradiation alone had no effect. In combination with 5-ALA, however, this illumination readily induced the death of all mouse and human melanoma cell lines examined. Still, 5-ALA PDT caused only minor focal regressive changes including haemorrhages and fibrosis of MT-ret melanomas in vivo and did not significantly delay tumour growth. These results show that, even though MT-ret melanoma cells are vulnerable to 5-ALA PDT in vitro, malignant MT-ret melanomas in vivo are quite resistant to this type of therapy at doses which are highly effective in vitro.
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PMID:5-aminolaevulinic acid photodynamic therapy in a transgenic mouse model of skin melanoma. 1588 78

In several randomized, controlled studies, the application of a standard preparation containing methyl-aminolevulinate (MAL; Metvix, Galderma, F), followed by red light irradiation proved effective and well tolerated in the treatment of actinic keratosis and basal cell carcinoma, and has now been approved for clinical use in European countries. A brand name aminolevulinic acid (ALA) solution (Levulan Kerastick, Dusa Pharmaceuticals Inc., Wilmington, MA) plus blue light exposure has been approved for the treatment of actinic keratosis in the USA. Randomized and controlled studies have shown that MAL as well as ALA are also effective in the treatment of Bowen's disease. In addition, a large and growing number of open studies or case reports have evaluated its use in the treatment of a broad range of other neoplastic, inflammatory and infectious skin diseases. However, efficacy and definite advantages over standard therapies remain to be clarified because the experimental design of these studies was often poor, the number of enrolled patients was generally low, and the follow-up was shorter than 12 months. However, these studies have suggested a few possible clinical applications worthy of further investigation. A growing number of laboratory and clinical findings suggest that several new synthetic sensitizers, besides ALA and MAL, may be helpful in the treatment of non-melanoma skin cancers, melanoma metastasis, and selected inflammatory and infective skin diseases. These compounds are deliverable intravenously, have short half-lives both in the blood and skin, and are highly efficient. However, they are as of yet not approved for clinical use.
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PMID:Photodynamic therapy: update 2006. Part 2: Clinical results. 1737 68

Photodynamic therapy (PDT) is a minimally invasive therapeutic modality approved for clinical treatment of several types of cancer and non-oncological disorders. In PDT, a compound with photosensitising properties (photosensitiser, PS) is selectively accumulated in malignant tissues. The subsequent activation of the PS by visible light, preferentially in the red region of the visible spectrum (lambda>or=600 nm), where tissues are more permeable to light, generates reactive oxygen species, mainly singlet oxygen ((1)O(2)), responsible for cytotoxicity of neoplastic cells and tumour regression. There are three main mechanisms described by which (1)O(2) contributes to the destruction of tumours by PDT: direct cellular damage, vascular shutdown and activation of immune response against tumour cells. The advantages of PDT over other conventional cancer treatments are its low systemic toxicity and its ability to selectively destroy tumours accessible to light. Therefore, PDT is being used for the treatment of endoscopically accessible tumours such as lung, bladder, gastrointestinal and gynaecological neoplasms, and also in dermatology for the treatment of non-melanoma skin cancers (basal cell carcinoma) and precancerous diseases (actinic keratosis). Photofrin, ALA and its ester derivatives are the main compounds used in clinical trials, though newer and more efficient PSs are being evaluated nowadays.
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PMID:Photodynamic therapy of cancer. Basic principles and applications. 1832 17

Photodynamic therapy (PDT) is a noninvasive therapy for non-melanoma skin cancer. The aim of this study was comparison of efficacy between fractioned versus single dose illumination in photodynamic therapy (PDT) of actinic keratosis (AK) and Bowen's disease (BD). Fifty-one patients (36 AK and 15 BD) were treated with PDT They were randomly arranged in two treatment groups. Group one included 26 patients (20 AK and 6 BD) that, after five hours of incubation with 20% 5-ALA, were treated with a single illumination of 100 Jcm(-2) at fluence rate of 30 mWcm(-2). Group two included 25 patients (16 AK and 9 BD) that, after 16 hours of incubation with 20% 5-ALA, were treated with two light fractions (50 plus 50 Jcm(-2)) at same fluence rate with dark interval of two hours between fractions. Twenty-four weeks later, a treated area was incubated for four hours again with 5-ALA in order to detect occult areas of abnormal skin with possible remaining tumor tissue. In case of fluorescence, histological examination was performed. In the group one, fluorescence at the end of the session was absent in 19 (73%) or very weak in 7 (27%). Residual tumor was found in 15 (75%) AK and in 4 (66.6%) BD. In the group two, fluorescence at the end of second session was more intense; in one patient (4%) was absent, very weak in 5 (20%) and weak in 19 (76%) of patients. In this group histology revealed remaining tumor tissue in only 2 (12.5%) AK and 2 (22.2%) BD. Among the patients in the first group, the remaining tumor tissue was significantly bigger (p=0.005). The treatment response with clearing of tumor tissue was significantly higher in fractionated illumination than in a single dose illumination group. Fractionated illumination scheme with 16 hours of incubation separated by two hours dark interval significantly improves the therapeutic outcome in tumor eradication.
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PMID:Fractionated illumination improves the outcome in the treatment of precancerous lesions with photodynamic therapy. 1913 10

Photodynamic therapy (PDT) is based on the association of a light source and light sensitive agents in order to cause the selective death of tumor cells. To evaluate topical 5-aminolaevulinic acid (5-ALA) and diode laser photodynamic single session therapy single session for non-melanoma skin cancer (NMSC), a long-term follow-up was performed. Nineteen Bowen's disease (BD) and 15 basal cell carcinoma (BCC) lesions were submitted to 6-h topical and occlusive 20% 5-ALA plus DMSO and EDTA, and later were exposed to 630 nm diode laser, 100 or 300 J cm(-2) dose. At 3 months tumor-free rate was 91.2% (31/34) whereas at 60 months, 57.7% (15/26), slightly higher in BCC (63.6%; 7/11). The relation between the reduction of the clinical response and the increase of tumor dimension observed at 18 months was lost at 60 months. The sBCC recurrence was earlier compared to the nBCC one. ALA-PDT offered important advantages: it is minimally invasive, an option for patients under risk of surgical complications; clinical feasibility; treatment of multiple lesions in only one session or lesions in poor healing sites and superior esthetical results. However, the recurrence rate increase after ALA-PDT diode laser single session can be observed at long-term follow-up, and the repetitive sessions, an additional advantage of the method, is strongly recommended. The clinical response and recurrence time seem to be related to the laser light dose and NMSC types/sub-types, thickness and dimension, which must be considered for the choice of the ALA-PDT.
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PMID:Long-term follow-up of topical 5-aminolaevulinic acid photodynamic therapy diode laser single session for non-melanoma skin cancer. 1993 53


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