RESUMEN
PURPOSE: Glioblastoma is a malignant and aggressive brain tumour that, although there have been improvements in the first line treatment, there is still no consensus regarding the best standard of care (SOC) upon its inevitable recurrence. There are novel adjuvant therapies that aim to improve local disease control. Nowadays, the association of intraoperative photodynamic therapy (PDT) immediately after a 5-aminolevulinic acid (5-ALA) fluorescence-guided resection (FGR) in malignant gliomas surgery has emerged as a potential and feasible strategy to increase the extent of safe resection and destroy residual tumour in the surgical cavity borders, respectively. OBJECTIVES: To assess the survival rates and safety of the association of intraoperative PDT with 5-ALA FGR, in comparison with a 5-ALA FGR alone, in patients with recurrent glioblastoma. METHODS: This article describes a matched-pair cohort study with two groups of patients submitted to 5-ALA FGR for recurrent glioblastoma. Group 1 was a prospective series of 11 consecutive cases submitted to 5-ALA FGR plus intraoperative PDT; group 2 was a historical series of 11 consecutive cases submitted to 5-ALA FGR alone. Age, sex, Karnofsky performance scale (KPS), 5-ALA post-resection status, T1-contrast-enhanced extent of resection (EOR), previous and post pathology, IDH (Isocitrate dehydrogenase), Ki67, previous and post treatment, brain magnetic resonance imaging (MRI) controls and surgical complications were documented. RESULTS: The Mantel-Cox test showed a significant difference between the survival rates (p = 0.008) of both groups. 4 postoperative complications occurred (36.6%) in each group. As of the last follow-up (January 2024), 7/11 patients in group 1, and 0/11 patients in group 2 were still alive. 6- and 12-months post-treatment, a survival proportion of 71,59% and 57,27% is expected in group 1, versus 45,45% and 9,09% in group 2, respectively. 6 months post-treatment, a progression free survival (PFS) of 61,36% and 18,18% is expected in group 1 and group 2, respectively. CONCLUSION: The association of PDT immediately after 5-ALA FGR for recurrent malignant glioma seems to be associated with better survival without additional or severe morbidity. Despite the need for larger, randomized series, the proposed treatment is a feasible and safe addition to the reoperation.
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Ácido Aminolevulínico , Neoplasias Encefálicas , Glioblastoma , Recurrencia Local de Neoplasia , Fotoquimioterapia , Cirugía Asistida por Computador , Humanos , Glioblastoma/cirugía , Glioblastoma/tratamiento farmacológico , Glioblastoma/diagnóstico por imagen , Ácido Aminolevulínico/uso terapéutico , Masculino , Neoplasias Encefálicas/cirugía , Neoplasias Encefálicas/tratamiento farmacológico , Neoplasias Encefálicas/diagnóstico por imagen , Femenino , Persona de Mediana Edad , Fotoquimioterapia/métodos , Recurrencia Local de Neoplasia/cirugía , Anciano , Estudios de Cohortes , Cirugía Asistida por Computador/métodos , Fármacos Fotosensibilizantes/uso terapéutico , Adulto , Estudios Prospectivos , Procedimientos Neuroquirúrgicos/métodosRESUMEN
Actinic keratosis (AK) is the most common pre-malignant cutaneous lesion of the skin, often associated with field cancerization. Daylight photodynamic therapy (DL-PDT) is used as treatment, showing good histological results. Reflectance confocal microscopy (RCM) may be useful as a non-invasive, real-time approach to monitor treatment, however, there is a lack of data on the correlation between RCM and histopathological findings in AK patients treated with DL-PDT. To correlate histological and RCM findings and evaluate the efficacy of DL-PDT in patients with AK and field cancerization treated with DL-PDT. Patients with field cancerization and a minimum of six AK lesions on the face were included in the study. A single session combining methyl aminolevulinate followed by two-hour daylight exposure of the face was performed. RCM and biopsy were performed before and after three months of the intervention to compare efficacy between patients using the Wilcoxon test, and concordance of the findings based on the different methods was analysed using the Kappa test. Twenty-four patients completed the study. An improvement in photodamage and a decrease in the number of AK lesions (45.3% reduction) was observed. Regression in atypia and dysplasia was observed via histopathology and RCM, however, there was poor agreement between the methods. No changes were observed after treatment for inflammation, fibroplasia and acantholysis. Concordance between histological and RCM findings was poor, suggesting that RCM cannot replace the histopathological examination, however, it may be used as an adjuvant test for follow-up of patients. Despite this, DL-PDT proved to be an effective method for treating AK.
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Queratosis Actínica , Fotoquimioterapia , Humanos , Queratosis Actínica/diagnóstico por imagen , Queratosis Actínica/tratamiento farmacológico , Queratosis Actínica/etiología , Fotoquimioterapia/métodos , Ácido Aminolevulínico/uso terapéutico , Inflamación , Protectores Solares/uso terapéutico , Microscopía Confocal/métodos , Fármacos Fotosensibilizantes/uso terapéutico , Resultado del TratamientoRESUMEN
The aim of the present study was to investigate the effects of PDT using the photosensitizer 5-aminoulevulinic acid (5-ALA) in oral squamous cell carcinoma (OSCC) behavior, mainly regarding its role on the cancer stem cell (CSC) phenotypes and in maintenance of the stem cell properties. Two OSCC cell lines were used and divided in the groups: Control, 5-ALA, LED 6 J/cm2 and PDT. MTT and Neutral red assays were used to access cellular viability, cell migration was evaluated by the wound healing assay. The stem cell phenotype was analyzed by flow cytometry to evaluate the CD44high/ESAhigh, CD44high/ESAlow and CD44low populations, by the clonogenic and tumor sphere formation assays as well as by RT-qPCR. The presence of Protoporphyrin IX in each CSC fraction was evaluated by flow cytometry. The OSCC cell lines showed a significant decrease in cell viability and migration after PDT. The percentage of CD44high/ESAhigh cells decreased after PDT, which was associated with an increase in the CD44low cells and with a functional decrease in the colony and sphere formation capacity. CD44high/ESAhigh cells showed increased PpIX, which contributed for their greater sensitivity to PDT. INV gene increased significantly after PDT, indicating cellular differentiation. Altogether, our results demonstrate that 5-ALA mediated PDT decreases not only the fraction of oral CSC but also their functional capabilities, inducing their differentiation.
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Carcinoma de Células Escamosas , Neoplasias de la Boca , Fotoquimioterapia , Ácido Aminolevulínico/farmacología , Ácido Aminolevulínico/uso terapéutico , Carcinoma de Células Escamosas/tratamiento farmacológico , Línea Celular Tumoral , Humanos , Neoplasias de la Boca/tratamiento farmacológico , Células Madre Neoplásicas/metabolismo , Rojo Neutro/uso terapéutico , Fotoquimioterapia/métodos , Fármacos Fotosensibilizantes/farmacología , Fármacos Fotosensibilizantes/uso terapéutico , Protoporfirinas/metabolismoRESUMEN
Photodynamic therapy (PDT) is a non-surgical treatment that has been approved for its human medical use in many cancers. PDT involves the interaction of a photosensitizer (PS) with light. The amino acid 5- aminolevulinic acid (ALA) can be used as a pro-PS, leading to the synthesis of Protoporphyrin IX. Hydrogen sulfide (H2S) is an endogenously produced gas that belongs to the gasotransmitter family, which can diffuse through biological membranes and have relevant physiological effects such as cardiovascular functions, vasodilatation, inflammation, cell cycle and neuro-modulation. It was also proposed to have cytoprotective effects. We aimed to study the modulatory effects of H2S on ALAPDT in the mammary adenocarcinoma cell line LM2. Exposure of the cells to NaHS (donor of H2S) in concentrations up to 10 mM impaired the response to ALA-PDT in a dose-dependent manner. The addition of 3 doses of NaHS showed the highest effect. This decreased response to the photodynamic treatment was correlated to an increase in the GSH levels, catalase activity, a dose dependent reduction of PpIX and increased intracellular ALA, decreased levels of oxidized proteins and a decrease of PDT-induced ROS. NaHS also reduced the levels of singlet oxygen in an in vitro assay. H2S also protected other cells of different origins against PDT mediated by ALA and other PSs. These results suggest that H2S has a role in the modulation of the redox state of the cells, and thus impairs the response to ALA-PDT through multifactor pathways. These findings could contribute to developing new strategies to improve the effectiveness of PDT particularly mediated by ALA or other ROS-related treatments.
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Sulfuro de Hidrógeno , Fotoquimioterapia , Ácido Aminolevulínico/farmacología , Ácido Aminolevulínico/uso terapéutico , Línea Celular Tumoral , Humanos , Sulfuro de Hidrógeno/farmacología , Oxidación-Reducción , Fotoquimioterapia/métodos , Fármacos Fotosensibilizantes/farmacología , Fármacos Fotosensibilizantes/uso terapéutico , Protoporfirinas/farmacología , Especies Reactivas de Oxígeno/metabolismoRESUMEN
BACKGROUND: Actinic keratosis (AK) are pre-malignant lesions, precursors of squamous cell carcinoma (SCC). Normal skin adjacent to AK, may present initial mutations with potential risk for new neoplasms, currently known today as field cancerization (FC). OBJECTIVES: To evaluate the effectiveness of daylight photodynamic therapy (PDT) with methyl amino levulinate (MAL) based on clinical evaluation, histological examination and immunohistochemical expression of p53 and Ki67. MATERIAL AND METHODS: Thirty patients, over 35 years old, phototypes between I and III, presenting non-hypertrophic AK on the face or scalp. Two biopsies with 2 mm punch of the lesion and adjacent skin before and 60 days after daylight PDT were performed. Results: Improvement was seen in lesion thickness and Ki67. 19 (63.33%) lesions had atypia improvement with a p-value <.05, showing efficacy in treatment. After daylight PDT, 22 (73.33%) patients showed satisfactory esthetic improvement. CONCLUSION: The study shows that PDT has cellular and molecular effects that support its indication in the control of carcinogenesis, as it decreases atypia and controls the expression of Ki67, reducing the proliferation of atypical cells. However, its indication following this study is still mainly aimed at clinical improvement of the skin, at this moment, probably due to the sample size.
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Queratosis Actínica , Fotoquimioterapia , Adulto , Ácido Aminolevulínico/uso terapéutico , Humanos , Queratosis Actínica/tratamiento farmacológico , Queratosis Actínica/patología , Fotoquimioterapia/efectos adversos , Fármacos Fotosensibilizantes/uso terapéutico , Cuero Cabelludo/patología , Resultado del TratamientoRESUMEN
OBJECTIVES: This is a randomized controlled clinical trial comparing Photodynamic Therapy (PDT) and the application of trichloracetic acid (TAA) in the treatment of HPV condyloma in the perianal and vulva regions. Design, Randomised controlled, open label, trial. They were allocated to each treatment following randomization by a computer program. SETTING: Women Health Ambulatory in São Carlos city, São Paulo State in the Brazil. PARTICIPANTS: 36 patients evaluated. 31 patients fulfilled the study requirements. INTERVENTION: Photodynamic Therapy (PDT) versus trichloracetic acid (TAA). The PDT protocol used the prodrug methyl aminolevulinate incubated for 3 hours and irradiation at 630 nm (100 J/cm²). In the treatment using TAA, warts received a small amount of acid using a cotton swab. Both treatments were repeated weekly until the lesions disappeared completely or until 10 sessions were completed. MAIN OUTCOME MEASURE: Clinical analysis. Follow-up between 12 and 30 months after the complete treatment. RESULTS: A total of 16 patients were treated with PDT and 15 patients with TAA. A complete response rate of 60% for TAA and 63% for PDT, with a recurrence rate of 33% for TAA and 0% for PDT. CONCLUSION: PDT appears not only to treat lesions due to physical destruction of condyloma and subclinical lesions, but also to modulate the immune system and/or also to decrease the local viral load, suggesting a lower recurrence compared to the TAA group.
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Condiloma Acuminado , Infecciones por Papillomavirus , Fotoquimioterapia , Ácido Aminolevulínico/uso terapéutico , Brasil , Condiloma Acuminado/tratamiento farmacológico , Femenino , Humanos , Infecciones por Papillomavirus/tratamiento farmacológico , Fotoquimioterapia/métodos , Fármacos Fotosensibilizantes/uso terapéutico , Ácido Tricloroacético/uso terapéuticoRESUMEN
The delta-amino acid 5-aminolevulinic acid (ALA), is the precursor of the endogenous photosensitiser Protoporphyrin IX (PpIX), and is currently approved for Photodynamic Therapy (PDT) of certain superficial cancers. However, ALA-PDT is not very effective in diseases in which T-cells play a significant role. Cutaneous T-cell lymphomas (CTCL) is a group of non-Hodgkin malignant diseases, which includes mycosis fungoides (MF) and Sézary syndrome (SS). In previous work, we have designed new ALA esters synthesised by three-component Passerini reactions, and some of them showed higher performance as compared to ALA. This work aimed to determine the efficacy as pro-photosensitisers of five new ALA esters of 2-hydroxy-N-arylacetamides (1f, 1 g, 1 h, 1i and 1 k) of higher lipophilicity than ALA in Myla cells of MF and HuT-78 cells of SS. We have also tested its effectiveness against ALA and the already marketed ALA methyl ester (Me-ALA) and ALA hexyl ester (He-ALA). Both cell Myla and SS cells were effectively and equally photoinactivated by ALA-PDT. Besides, the concentration of ALA required to induce half the maximal porphyrin synthesis was 209 µM for Myla and 169 µM for HuT-78 cells. As a criterion of efficacy, we calculated the concentration of the ALA derivatives necessary to induce half the plateau porphyrin values obtained from ALA. These values were achieved at concentrations 4 and 12 times lower compared to ALA, according to the derivative used. For He-ALA, concentrations were 24 to 25 times lower than required for ALA for inducing comparable porphyrin synthesis in both CTCL cells. The light doses for inducing 50% of cell death (LD50) for He-ALA, 1f, 1 g, 1 h and 1i were around 18 and 25 J/cm2 for Myla and HuT-78 cells respectively, after exposure to 0.05 mM concentrations of the compounds. On the other hand, the LD50s for the compound 1 k were 40 and 57 J/cm2 for Myla and HuT-78, respectively. In contrast, 0.05 mM of ALA and Me-ALA did not provoke photokilling since the concentration employed was far below the porphyrin saturation point for these compounds. Our results suggest the potential use of ALA derivatives for topical application in PDT treatment of MF and extracorporeal PDT for the depletion of activated T-cells in SS.
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Ácido Aminolevulínico/análogos & derivados , Fármacos Fotosensibilizantes/farmacología , Ácido Aminolevulínico/farmacología , Ácido Aminolevulínico/uso terapéutico , Línea Celular Tumoral , Supervivencia Celular/efectos de los fármacos , Supervivencia Celular/efectos de la radiación , Humanos , Luz , Linfocitos/efectos de los fármacos , Linfocitos/metabolismo , Linfocitos/fisiología , Fotoquimioterapia , Fármacos Fotosensibilizantes/química , Fármacos Fotosensibilizantes/uso terapéuticoRESUMEN
Photodynamic Therapy (PDT) is a therapeutic modality used for several malignant and premalignant skin disorders, including Bowen's disease skin cancers and Superficial Basal Cell Carcinoma (BCC). Several photosensitizers (PSs) have been explored for tumor destruction of skin cancers, after their activation by a light source of appropriate wavelength. Topical release of PSs avoids prolonged photosensitization reactions associated with systemic administration; however, its clinical usefulness is influenced by its poor tissue penetration and the stability of the active agent. Nanotechnology-based drug delivery systems are promising tool to enhance the efficiency for PDT of cancer. This review focuses on PSs encapsulated in nanocarriers explored for PDT of skin tumors.
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Enfermedad de Bowen , Carcinoma Basocelular , Portadores de Fármacos , Nanopartículas , Fotoquimioterapia , Neoplasias Cutáneas , Ácido Aminolevulínico/uso terapéutico , Enfermedad de Bowen/tratamiento farmacológico , Carcinoma Basocelular/tratamiento farmacológico , Humanos , Fármacos Fotosensibilizantes/uso terapéutico , Neoplasias Cutáneas/tratamiento farmacológicoRESUMEN
INTRODUCTION: Skin neoplasms are the most frequent malignant lesions, increasing patient's morbidity when associated with skin field cancerisation. There is a need to understand the current therapies, both clinical and surgical. METHODS: A systematic review was performed according to the PRISMA guideline, registered in PROSPERO: CRD42018114826, including studies from 2012 to 2019. RESULTS: Seven hundred and eighty-two studies were found, of which 21 were included. Of these, 8 primary studies were randomised controlled trials: fractional CO2 laser-assisted photodynamic therapy (PDT) vs. PDT (no significance), daylight PDT vs. PDT (no significance, daylight PDT had less adverse effects), trichloroacetic acid peel vs. 5-aminolaevulinic acid PDT (clinical improvement of aminolaevulinic acid PDT), 5-Fluorouracil 0.5%/Salicylic Acid 10% vs. vehicle (clinical improvement of 5-Fluorouracil 0.5%/Salicylic Acid 10%), photolyase vs. sun filters (no significance), sunscreens vs. sunscreens plus DNA repair enzymes (DNA Repair Enzymes was more effective in reducing field cancerisation). Only one systematic review was included in which there was effectiveness of daylight PDT in the treatment of actinic keratoses. The other 12 included studies had a lower level of evidence including surgical studies. CONCLUSION: Clinical studies are more relevant in the treatment of the field cancerisation. There is a lack of surgical studies.
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Queratosis Actínica , Fotoquimioterapia , Ácido Aminolevulínico/uso terapéutico , Humanos , Queratosis Actínica/tratamiento farmacológico , Fármacos Fotosensibilizantes/uso terapéutico , Protectores Solares , Resultado del TratamientoRESUMEN
Glioblastoma is the most severe form of brain cancer. Despite multimodal therapy combining surgery, radiotherapy and chemotherapy, prognosis of patients is dismal. It has been observed that the surgical resection guided by photosensitizer fluorescence followed by photodynamic therapy (PDT) prolongs the average survival in patients with glioblastoma. The main problem with all oncological treatments, including PDT, is the presence of resistant cells. The objective of this study was to isolate and perform an initial characterization of human glioblastoma cells resistant to PDT employing methyl-5-aminolevulinic acid. We obtained resistant cells from the T98 G cell line. Resistant populations accumulated less photosensitizer, formed spheroids of higher number of cells, had higher tumorigenic capacity, and expressed higher mRNA levels of fibroblastic growth factor receptor (FGFR), epidermal growth factor receptor (EGFR) and ß-platelet-derived growth factor receptor (ßPDGFR) than parental cells. The studies of glioblastoma resistance to PDT would help to better understand the causes of tumor recurrence after PDT and to develop new therapeutic proposals in this field of oncology.
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Glioblastoma , Fotoquimioterapia , Ácido Aminolevulínico/farmacología , Ácido Aminolevulínico/uso terapéutico , Línea Celular Tumoral , Glioblastoma/tratamiento farmacológico , Humanos , Recurrencia Local de Neoplasia , Fotoquimioterapia/métodos , Fármacos Fotosensibilizantes/farmacología , Fármacos Fotosensibilizantes/uso terapéuticoRESUMEN
BACKGROUND: Nanoparticles show promise for theranostic applications in cancer. The metal-based nanoparticles can be used both as photosensitizers and delivery vehicles. In bimetallic particles based on gold or silver and iron, a combination of the plasmonic features of the gold or silver components with the magnetic properties of the iron makes these hybrid nanomaterials suitable for both imaging and therapeutic applications. Herein, we discuss toxicity and cell internalization of metallic (silver and gold) and bimetallic (silver-iron, gold-iron, and silver-gold) aminolevulinic acid (ALA) nanoparticles. ALA can control the production of an intracellular photosensitizer, protoporphyrin IX (PpIX), commonly used in photodynamic therapy. METHODS: Nanoparticles were synthesized by photoreduction method and characterized by UV/Vis spectra, Zeta potential, FTIR, XRD, and transmission electron microscopy. The amount of singlet oxygen generation by a yellow LED, and ultrasound was studied for gold, gold-iron, and silver-gold nanoparticles. Cytotoxicity assays of MCF-7 in the presence of nanoparticles were performed, and PpIX fluorescence was quantified by high content screening (HCS). RESULTS: Red fluorescence observed after 24â¯h of nanoparticles incubation on MCF-7 cells, indicated that the ALA in surface of nanoparticles was efficiently converted to PpIX. The best results for singlet oxygen generation with LED or ultrasound irradiation were obtained with ALA:AgAuNPs. CONCLUSIONS: The studied nanoparticles present the potential to deliver aminolevulinic acid to breast cancer cells efficiently, generate singlet oxygen, and convert ALA into PpIX inside the cells allowing photodiagnosis and therapies such as photodynamic and sonodynamic therapies.
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Neoplasias de la Mama , Nanopartículas del Metal , Fotoquimioterapia , Ácido Aminolevulínico/farmacología , Ácido Aminolevulínico/uso terapéutico , Neoplasias de la Mama/tratamiento farmacológico , Línea Celular Tumoral , Oro/uso terapéutico , Humanos , Hierro/uso terapéutico , Células MCF-7 , Fotoquimioterapia/métodos , Fármacos Fotosensibilizantes/farmacología , Fármacos Fotosensibilizantes/uso terapéutico , Protoporfirinas/uso terapéutico , PlataRESUMEN
High-grade cervical intraepithelial neoplasia (CIN) is the precursor to cervical cancer. HPV (human papillomavirus) infection is strongly related with this disease. The CIN treatment is generally excision of the transformation zone (ETZ). Photodynamic therapy (PDT) has also shown to be a promising treatment. We are reporting a case of a 33-years-old patient with high-grade CIN 3 treated with topical MAL (methyl aminolevulinate) PDT. Was applied 2.5 g of 20 % (w/w) MAL cream overnight and the cervix was illuminated twice, with three weeks apart, using a probe with LEDs simultaneously with a cylindrical laser fiber emitting both at 630 nm, with a fluency of 150 J/cm2. CIN 3 and the presence of high-risk HPV virus was eliminated 120 days after the second procedure. There was no recurrence at 6 months follow-up. This case report using MAL-PDT and a different light arrangement with LEDs and laser fiber associated both cured the patient with CIN 3 and eliminated low and high-risk HPV in just two PDT sessions.
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Infecciones por Papillomavirus , Fotoquimioterapia , Displasia del Cuello del Útero , Neoplasias del Cuello Uterino , Adulto , Ácido Aminolevulínico/uso terapéutico , Femenino , Humanos , Recurrencia Local de Neoplasia/tratamiento farmacológico , Infecciones por Papillomavirus/tratamiento farmacológico , Fotoquimioterapia/métodos , Fármacos Fotosensibilizantes/uso terapéutico , Neoplasias del Cuello Uterino/tratamiento farmacológico , Displasia del Cuello del Útero/tratamiento farmacológicoRESUMEN
Aim: Nano-5-aminolevulic acid (NanoALA)-mediated photodynamic therapy (PDT), an oil-in-water polymeric nanoemulsion of ALA, was evaluated in a murine model of breast cancer. Materials & methods: Analysis of ALA-derived protoporphyrin IX production and acute toxicity test, biocompatibility and treatment efficacy, and long-term effect of NanoALA-PDT on tumor progression were performed. Results: The nanoformulation favored the prodrug uptake by tumor cells in a shorter time (1.5 h). As a result, the adverse effects were negligible and the response rates for primary mammary tumor control were significantly improved. Tumor progression was slower after NanoALA-PDT treatment, providing longer survival. Conclusion: NanoALA is a good proactive drug candidate for PDT against cancer potentially applied as adjuvant/neoadjuvant intervention strategy for breast cancer.
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Ácido Aminolevulínico/uso terapéutico , Neoplasias de la Mama , Fotoquimioterapia , Animales , Neoplasias de la Mama/tratamiento farmacológico , Muerte Celular , Línea Celular Tumoral , Portadores de Fármacos , Humanos , Ratones , Nanomedicina , Fármacos Fotosensibilizantes/uso terapéuticoRESUMEN
The objective of this study was to evaluate and compare the clinical response to PDT (Photodynamic Therapy) in field cancerization using two aminolevulinate derivatives. Forty patients with multiple actinic keratosis (AK) on forearms and hands scattered received two sessions of ALA and MAL-PDT at 630â¯nm (36â¯J/cm2). The AK clearance rate was 72 % for both drugs with a significant decrease in AK observed clinically (pâ¯<â¯00,001). Clinical improvement in field cancerization using two aminolevulinate derivatives in PDT is proven with no significant difference in the efficacy of drugs.
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Queratosis Actínica , Fotoquimioterapia , Ácido Aminolevulínico/uso terapéutico , Humanos , Queratosis Actínica/tratamiento farmacológico , Fotoquimioterapia/métodos , Fármacos Fotosensibilizantes/uso terapéutico , Resultado del TratamientoRESUMEN
BACKGROUND: Laser-assisted MAL-PDT has been reported to increase the effectiveness of conventional PDT. Nonetheless, clinical effects of this association when reducing MAL incubation time is poorly discussed. Furthermore, the association of acoustic pressure wave ultrasound with laser-assisted MAL-PDT with short incubation time for field cancerization had not been reported before. OBJECTIVES: To compare clinical effects of ablative fractional laser-assisted MAL-PDT associated with acoustic pressure wave ultrasound (IMPACT US) with 1-hour incubation time and conventional MAL-PDT for skin field cancerization on the forearms, as well as the impact on safety and tolerability. METHODS: Fifteen patients with 638 AK (grade I-III) with field cancerized-skin on the forearms were enrolled in this left-right trial. Two protocols were randomly chosen. One side was treated with conventional MAL-PDT, whereas the other with laser-assisted MAL-PDT associated with acoustic pressure wave ultrasound with 1-hour incubation time. Actinic keratoses were quantitively measured, and the other signs of sun-damaged skin, like pigmentation and texture, in field cancerized skin were qualitatively evaluated before and after six months. Side effects were assessed subjectively during the procedure and one week after. RESULTS: All patients completed the study. At six months after treatment, both protocols reduced the number of AK (72%; CO2â¯+â¯PDT, and 65%; MAL-PDT). The difference between these two protocols was not statistically significant (pâ¯=â¯0.77). The improvement of pigmentation and texture of field cancerized skin was more significant on the side treated with laser-assisted MAL-PDT associated with acoustic pressure wave ultrasound. Both protocols were well tolerated and without significant difference in adverse events. CONCLUSION: Laser-assisted MAL-PDT using CO2 laser and acoustic pressure wave ultrasound with short incubation time of 1â¯h was as effective as conventional MAL-PDT for field-cancerized skin with actinic keratosis in forearms with better cosmetic outcome.
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Ácido Aminolevulínico/análogos & derivados , Diagnóstico por Imagen de Elasticidad/métodos , Queratosis Actínica/terapia , Láseres de Gas/uso terapéutico , Fármacos Fotosensibilizantes/uso terapéutico , Neoplasias Cutáneas/terapia , Adulto , Anciano , Ácido Aminolevulínico/uso terapéutico , Terapia Combinada , Femenino , Antebrazo , Humanos , Queratosis Actínica/tratamiento farmacológico , Masculino , Persona de Mediana Edad , Fotoquimioterapia , Neoplasias Cutáneas/tratamiento farmacológico , Ondas UltrasónicasRESUMEN
Objective: In this study, we evaluated the effectiveness of photodynamic therapy (PDT) for the treatment of experimental cutaneous leishmaniasis (CL) and the profile of macrophages activation markers. Background: Leishmaniasis is an infectious disease caused by parasites of the genus Leishmania. CL is caused by Leishmania major in the old world and by Leishmania braziliensis in the Americas. Considering the targeted organs, PDT may constitute a valuable therapeutic intervention. Macrophages are the host cells of Leishmania in mammals and may be classified into type M1 or M2 depending on the pattern of activation. Methods: BALB/c mice were infected in the foot pad with 1 × 106 amastigotes of L. braziliensis and treated with 5-aminolevulinic acid (5-ALA), visible light, or 5-ALA-PDT. The ex vivo mRNA expression levels of interleukin-10, tumor necrosis factor-α (TNF-α), arginase-1, heme oxygenase ( Hmox), and induced nitric oxide synthase (iNOS) were quantities as markers of macrophage activation with distinct ability to kill intracellular parasite. Results: The parasite load decreased significantly in the group treated with PDT compared with the other groups. The iNOS relative mRNA was higher in the group treated with PDT and light only compared with the group without treatment, whereas iNOS/arginase ratio was significantly higher only in the PDT group. The expression of TNF-α was significantly higher in 5-ALA and light compared with PDT and control group. No significant difference was observed in the expression of the other markers evaluated. Conclusions: Both, light and 5-ALA-PDT were able to upregulate iNOS expression only; 5-ALA-PDT was able to reduce parasite burden. The increase in the iNOS levels suggests it might participate in the antimicrobial mechanisms triggered by 5-ALA-PDT; although parasite death mechanism was not completely clarified, the results presented in this study suggest that macrophage activation may contribute to parasite control.
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Ácido Aminolevulínico/uso terapéutico , Leishmaniasis Cutánea/terapia , Activación de Macrófagos/efectos de la radiación , Fotoquimioterapia , Fármacos Fotosensibilizantes/uso terapéutico , Animales , Modelos Animales de Enfermedad , Interleucina-10/metabolismo , Leishmaniasis Cutánea/metabolismo , Leishmaniasis Cutánea/patología , Masculino , Ratones , Ratones Endogámicos BALB C , Carga de Parásitos , Factor de Necrosis Tumoral alfa/metabolismoRESUMEN
Expression of proteins related to cell surveillance has been described in tumors presenting resistance to photodynamic therapy (PDT). The aim of this study was to verify whether there was upregulation of proteins related to resistance in oral squamous cell carcinoma (OSCC) after PDT. OSCC was chemically induced in rats and treated after one cycle of PDT mediated by 5-aminolevulinic acid (5-ALA-PDT). Immunolabeling of p-NFκB, Bcl-2, survivin, iNOS, p-Akt, p-mTOR and cyclin D1 was performed after the treatment. There was increased expression of Bcl-2 (P = 0.008), iNOS (P = 0.020), p-Akt (P = 0.020) and p-mTOR (P = 0.010) by surviving neoplastic cells after PDT when compared to the control. In conclusion, after one cycle of 5-ALA-mediated PDT, Bcl-2, p-Akt, p-mTOR and iNOS were upregulated in neoplastic cells of OSCC, suggesting an activation of antiapoptosis and cell proliferation pathways. This fact must be considered in the establishment of PDT protocols for OSCC treatment, mainly those in which PDT will be combined with chemotherapy drugs targeted at the studied proteins.
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Ácido Aminolevulínico/uso terapéutico , Carcinoma de Células Escamosas/tratamiento farmacológico , Neoplasias de la Boca/tratamiento farmacológico , Fotoquimioterapia , Fármacos Fotosensibilizantes/uso terapéutico , Carcinoma de Células Escamosas/metabolismo , Humanos , Neoplasias de la Boca/metabolismoRESUMEN
BACKGROUND: The primary clinical manifestation of skin field cancerization is the presence of actinic keratoses (AKs). Current treatments for AKs related to skin field cancerization include photodynamic therapy (PDT) and colchicine. The objective of this study is to evaluate the efficacy and safety of 0.5% colchicine cream versus PDT with methyl aminolevulinate (MAL-PDT) in the treatment of skin field cancerization. METHODS: In a randomized controlled and open clinical trial with a blind histopathological and immunohistochemical analysis, 36 patients with up to 10 AKs on their forearms will be included from the outpatient clinic. The forearms will be randomized into two groups, clinically evaluated and biopsied for histopathology and immunohistochemistry (p53 and Ki67). One forearm will be treated with 0.5% colchicine cream for 10 days, and the other forearm will receive one session of MAL-PDT; the forearms will subsequently be reassessed clinically and histologically after 60 days (T60) of treatment. The primary endpoint will be the point of complete clearance of AKs in T60. The sample size will enable a detection in the reduction of over 10% in AK counts between the groups with power of 0.9 and an alpha of 0.05, accounting for an estimated dropout rate of 10%, resulting in 36 patients (72 forearms). All participants included in the randomized study will be part of the analysis, and the final outcomes of any dropouts will be the value of their last visit (LOCF). The statistical analysis will be performed using SPSS 22.0, and a p value < 5% will be considered to be significant. DISCUSSION: It is expected that colchicine will be superior to MAL-PDT in reducing AKs and in the skin field cancerization, and there will be good tolerability in both groups. Colchicine intervention is novel in that it provides a new alternative to MAL-PDT. Moreover, this drug is inexpensive that may be a potential treatment of skin field cancerization that can be prescribed in public health systems with good results. TRIAL REGISTRATION: The trial is registered in Brazilian Registry for Clinical Trials (Registration number: RBR-8y3sj9 , date assigned May 4, 2016, retrospectively registered).
Asunto(s)
Ácido Aminolevulínico/análogos & derivados , Protocolos Clínicos , Colchicina/administración & dosificación , Queratosis Actínica/terapia , Fotoquimioterapia , Fármacos Fotosensibilizantes/uso terapéutico , Crema para la Piel/administración & dosificación , Ácido Aminolevulínico/uso terapéutico , Humanos , Queratosis Actínica/patología , Lesiones Precancerosas , Ensayos Clínicos Controlados Aleatorios como AsuntoRESUMEN
CONTEXT: 5-Aminolevulinic acid (5-ALA) is a prodrug used in photodynamic therapy (PDT) of tumors, including cancer of the oral mucosa. 5-ALA poorly penetrates oral tissues due to its high hydrophilicity, which impairs its local effects in PDT. OBJECTIVES: To examine whether α-bisabolol (α-Bis) influences the 5-ALA permeability in the porcine buccal mucosa, to an extent that improves its application in PDT (which requires low permeation and high retention in the buccal mucosa). METHODS: In vitro permeability studies with 5-ALA (1% and 10% w/w) associated with α-Bis (1% to 20% w/w) in propylene glycol were carried out at 4h and 24h using porcine buccal mucosa in a modified Franz cell system. The in vitro release profiles (0.5 to 48h) of the selected formulation and its respective control were determined using artificial membranes. Samples of buccal mucosa treated with the formulation were submitted to histopathological analysis, using a routine optical microscopy technique. RESULTS: The association of 1% 5-ALA and 5% α-Bis provided the best results; after 4h of treatment with this formulation, the 5-ALA permeation was low and its retention in the mucosa was six-fold higher than that promoted by the control formulation (5-ALA alone). Histological analysis of the porcine buccal mucosa evidenced that 5% α-Bis altered the tissue morphology, which probably promoted 5-ALA retention. We concluded that 5% α-Bis is a potential adjuvant in formulations containing 5-ALA that could improve its retention after topical oral administration for the PDT treatment of cancer.