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1.
Int J Mol Sci ; 24(14)2023 Jul 10.
Artigo em Inglês | MEDLINE | ID: mdl-37511049

RESUMO

Photodynamic therapy (PDT) has shown improvements in cancer treatment and in the induction of a proper anti-tumor immune response. However, current photosensitizers (PS) lack tumor specificity, resulting in reduced efficacy and side effects in patients with intraperitoneal ovarian cancer (OC). In order to target peritoneal metastases of OC, which overexpress folate receptor (FRα) in 80% of cases, we proposed a targeted PDT using a PS coupled with folic acid. Herein, we applied this targeted PDT in an in vivo mouse model of peritoneal ovarian carcinomatosis. The efficacy of the treatment was evaluated in mice without and with human peripheral blood mononuclear cell (PBMC) reconstitution. When mice were reconstituted, using a fractionized PDT protocol led to a significantly higher decrease in the tumor growth than that obtained in the non-reconstituted mice (p = 0.0469). Simultaneously, an immune response was reflected by an increase in NK cells, and both CD4+ and CD8+ T cells were activated. A promotion in cytokines IFNγ and TNFα and an inhibition in cytokines TGFß, IL-8, and IL-10 was also noticed. Our work showed that a fractionized FRα-targeted PDT protocol is effective for the treatment of OC and goes beyond local induction of tumor cell death, with the promotion of a subsequent anti-tumor response.


Assuntos
Neoplasias Ovarianas , Neoplasias Peritoneais , Fotoquimioterapia , Humanos , Camundongos , Animais , Feminino , Leucócitos Mononucleares/metabolismo , Fotoquimioterapia/métodos , Neoplasias Ovarianas/metabolismo , Fármacos Fotossensibilizantes/farmacologia , Fármacos Fotossensibilizantes/uso terapêutico , Neoplasias Peritoneais/secundário , Citocinas/metabolismo , Ácido Fólico/uso terapêutico , Linhagem Celular Tumoral , Receptor 1 de Folato/metabolismo , Receptor 1 de Folato/uso terapêutico
2.
Int J Mol Sci ; 24(13)2023 Jun 21.
Artigo em Inglês | MEDLINE | ID: mdl-37445603

RESUMO

Photodynamic therapy (PDT) is a two-stage treatment relying on cytotoxicity induced by photoexcitation of a nontoxic dye, called photosensitizer (PS). Using 5-aminolevulinic acid (5-ALA), the pro-drug of PS protoporphyrin IX, we investigated the impact of PDT on hepatocellular carcinoma (HCC). Optimal 5-ALA PDT dose was determined on three HCC cell lines by analyzing cell death after treatment with varying doses. HCC-patient-derived tumor hepatocytes and healthy donor liver myofibroblasts were treated with optimal 5-ALA PDT doses. The proliferation of cancer cells and healthy donor immune cells cultured with 5-ALA-PDT-treated conditioned media was analyzed. Finally, therapy efficacy on humanized SCID mice model of HCC was investigated. 5-ALA PDT induced a dose-dependent decrease in viability, with an up-to-four-fold reduction in viability of patient tumor hepatocytes. The 5-ALA PDT treated conditioned media induced immune cell clonal expansion. 5-ALA PDT has no impact on myofibroblasts in terms of viability, while their activation decreased cancer cell proliferation and reduced the tumor growth rate of the in vivo model. For the first time, 5-ALA PDT has been validated on primary patient tumor hepatocytes and donor healthy liver myofibroblasts. 5-ALA PDT may be an effective anti-HCC therapy, which might induce an anti-tumor immune response.


Assuntos
Carcinoma Hepatocelular , Neoplasias Hepáticas , Transplante de Fígado , Fotoquimioterapia , Camundongos , Animais , Humanos , Ácido Aminolevulínico/farmacologia , Ácido Aminolevulínico/uso terapêutico , Carcinoma Hepatocelular/tratamento farmacológico , Meios de Cultivo Condicionados/farmacologia , Neoplasias Hepáticas/tratamento farmacológico , Camundongos SCID , Doadores Vivos , Fármacos Fotossensibilizantes/farmacologia , Fármacos Fotossensibilizantes/uso terapêutico , Protoporfirinas/metabolismo , Linhagem Celular Tumoral
3.
Molecules ; 24(7)2019 Apr 11.
Artigo em Inglês | MEDLINE | ID: mdl-30978982

RESUMO

The search for biomarkers in our solar system is a fundamental challenge for the space research community. It encompasses major difficulties linked to their very low concentration levels, their ambiguous origins (biotic or abiotic), as well as their diversity and complexity. Even if, in 40 years' time, great improvements in sample pre-treatment, chromatographic separation and mass spectrometry detection have been achieved, there is still a need for new in situ scientific instrumentation. This work presents an original liquid chromatographic system with a trapping unit dedicated to the one-pot detection of a large set of non-volatile extra-terrestrial compounds. It is composed of two units, monitored by a single pump. The first unit is an online trapping unit able to trap polar, apolar, monomeric and polymeric organics. The second unit is an online analytical unit with a high-resolution Q-Orbitrap mass spectrometer. The designed single pump system was as efficient as a laboratory dual-trap LC system for the analysis of amino acids, nucleobases and oligopeptides. The overall setup significantly improves sensitivity, providing limits of detection ranging from ppb to ppt levels, thus meeting with in situ enquiries.


Assuntos
Biomarcadores/química , Cromatografia Líquida , Compostos Orgânicos/química , Sistema Solar/química , Aminoácidos/química , Humanos , Espectrometria de Massas em Tandem
4.
Lasers Surg Med ; 50(5): 460-468, 2018 07.
Artigo em Inglês | MEDLINE | ID: mdl-29023876

RESUMO

BACKGROUND: High-grade gliomas are primary brain tumors that have shown increasing incidence and unfavorable outcomes. Local control is crucial to the management of this pathology. Photodynamic therapy (PDT), based on the light-induced activation of a photosensitizer (PS), achieves local treatment by inducing selective lesions in tumor tissue. OBJECTIVES: Previous studies have reported the outcomes of PDT for glioblastoma via immunohistological data. Our study aimed to evaluate MRI findings, including diffusion, and perfusion sequences, compared with immunohistological data from the same population to address the efficiency of light fractionation. MATERIALS AND METHODS: Twenty-six "nude" rats grafted with human U87 cells into the right putamen underwent PDT. After PS precursor (5-ALA) intake, an optical fiber was introduced into the tumor. The rats were randomized into the following groups: those without illumination and those that received two or five fractions of light. Treatment effects were assessed with early high-field MRI to measure the volume of necrosis and edema using diffusion and perfusion sequences; the MRI results were compared with immunohistology results, including necrosis and apoptosis markers. RESULTS: Elevated diffusion values were observed on MRI in the centers of the tumors of the treated animals, especially in the 5-fraction group (P < 0.01). Perfusion was decreased around the treatment site, especially in the 5-fraction group (P = 0.024). The MRI findings were consistent with previously published histological data. The median volume of necrosis was significantly different between the sham group and treated groups, 0 mm3 versus 2.67 mm3 , P < 0.001. The same trend was previously observed in histology data when grading the absence or presence of necrosis and when the presence of necrosis was significantly more predominant for the treated group than for the untreated group (P < 001). Additionally, cell death represented by apoptosis marker data (TUNEL method) was significantly higher in the 5-fraction group than in the 2-fraction group (P = 0.01). CONCLUSION: Diffusion and perfusion MRI revealed histological lesions. Interstitial PDT (iPDT) induced specific lesions in the tumor tissue, which were observed with MRI and confirmed by histopathological analysis. Thus, MRI may provide a non-invasive and reliable tool to assess treatment outcomes after PDT. Lasers Surg. Med. 50:460-468, 2018. © 2017 Wiley Periodicals, Inc.


Assuntos
Neoplasias Encefálicas/diagnóstico por imagem , Neoplasias Encefálicas/tratamento farmacológico , Glioma/diagnóstico por imagem , Glioma/tratamento farmacológico , Imageamento por Ressonância Magnética , Fotoquimioterapia , Ácido Aminolevulínico/uso terapêutico , Animais , Neoplasias Encefálicas/patologia , Modelos Animais de Doenças , Glioma/patologia , Fármacos Fotossensibilizantes/uso terapêutico , Ratos , Ratos Nus , Reprodutibilidade dos Testes
5.
Lasers Surg Med ; 49(5): 506-515, 2017 07.
Artigo em Inglês | MEDLINE | ID: mdl-28012197

RESUMO

BACKGROUND: Glioblastoma is a high-grade cerebral tumor with local recurrence and poor outcome. Photodynamic therapy (PDT) is a localized treatment based on the light activation of a photosensitizer (PS) in the presence of oxygen, which results in the formation of cytotoxic species. The delivery of fractionated light may enhance treatment efficacy by reoxygenating tissues. OBJECTIVE: To evaluate the efficiency of two light-fractionation schemes using immunohistological data. MATERIALS AND METHODS: Human U87 cells were grafted into the right putamen of 39 nude rats. After PS precursor intake (5-ALA), an optic fiber was introduced into the tumor. The rats were randomly divided into three groups: without light, with light split into 2 fractions and with light split into 5 fractions. Treatment effects were assessed using brain immunohistology. RESULTS: Fractionated treatments induced intratumoral necrosis (P < 0.001) and peritumoral edema (P = 0.009) associated with a macrophagic infiltration (P = 0.006). The ratio of apoptotic cells was higher in the 5-fraction group than in either the sham (P = 0.024) or 2-fraction group (P = 0.01). Peripheral vascularization increased after treatment (P = 0.017), and these likely new vessels were more frequently observed in the 5-fraction group (P = 0.028). CONCLUSION: Interstitial PDT with fractionated light resulted in specific tumoral lesions. The 5-fraction scheme induced more apoptosis but led to greater peripheral neovascularization. Lasers Surg. Med. 49:506-515, 2017. © 2016 Wiley Periodicals, Inc.


Assuntos
Ácido Aminolevulínico/uso terapêutico , Neoplasias Encefálicas/tratamento farmacológico , Glioblastoma/tratamento farmacológico , Fotoquimioterapia , Fármacos Fotossensibilizantes/uso terapêutico , Animais , Neoplasias Encefálicas/patologia , Modelos Animais de Doenças , Fracionamento da Dose de Radiação , Glioblastoma/patologia , Ratos , Ratos Nus
6.
J Extracell Vesicles ; 12(12): e12390, 2023 12.
Artigo em Inglês | MEDLINE | ID: mdl-38117000

RESUMO

Nasopharyngeal carcinoma-derived small extracellular vesicles (NPCSEVs) have an immunosuppressive impact on the tumour microenvironment. In this study, we investigated their influence on the generation of tolerogenic dendritic cells and the potential involvement of the galectin-9 (Gal9) they carry in this process. We analysed the phenotype and immunosuppressive properties of NPCSEVs and explored the ability of DCs exposed to NPCSEVs (NPCSEV-DCs) to regulate T cell proliferation. To assess their impact at the pathophysiological level, we performed real-time fluorescent chemoattraction assays. Finally, we analysed phenotype and immunosuppressive functions of NPCSEV-DCs using a proprietary anti-Gal9 neutralising antibody to assess the role of Gal9 in this effect. We described that NPCSEV-DCs were able to inhibit T cell proliferation despite their mature phenotype. These mature regulatory DCs (mregDCs) have a specific oxidative metabolism and secrete high levels of IL-4. Chemoattraction assays revealed that NPCSEVs could preferentially recruit NPCSEV-DCs. Finally, and very interestingly, the reduction of the immunosuppressive function of NPCSEV-DCs using an anti-Gal9 antibody clearly suggested an important role for vesicular Gal9 in the induction of mregDCs. These results revealed for the first time that NPCSEVs promote the emergence of mregDCs using a galectin-9 dependent mechanism and open new perspectives for antitumour immunotherapy targeting NPCSEVs.


Assuntos
Vesículas Extracelulares , Neoplasias Nasofaríngeas , Humanos , Carcinoma Nasofaríngeo , Células Dendríticas , Galectinas/metabolismo , Neoplasias Nasofaríngeas/metabolismo , Microambiente Tumoral
7.
Anesthesiology ; 114(1): 105-10, 2011 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-21169803

RESUMO

BACKGROUND: Difficult intubation management algorithms have proven efficacy in operating rooms but have rarely been assessed in a prehospital emergency setting. We undertook a prospective evaluation of a simple prehospital difficult intubation algorithm. METHODS: All of our prehospital emergency physicians and nurse anesthetists were asked to adhere to a simple algorithm in all cases of impossible laryngoscope-assisted tracheal intubation. They received a short refresher course and training in the use of the gum elastic bougie (GEB) and the intubating laryngeal mask airway (ILMA), which were techniques to be used as a first and a second step, respectively. In cases of difficult ventilation with arterial desaturation, IMLA was to be used first. Cricothyroidotomy was the ultimate rescue technique when ventilation through ILMA failed. Patient characteristics, adherence to the algorithm, management efficacy, and early complications were recorded (August 2005-December 2009). RESULTS: An alternative technique to secure the airway was needed in 160 of 2,674 (6%) patients undergoing intubation. Three instances of nonadherence to the algorithm were recorded. GEB was used first in 152 patients and was successful in 115. ILMA was used first in 8 patients and second in the 37 GEB-assisted intubation failures. Forty-five patients were successfully mask-ventilated, and 42 were blindly intubated before reaching the hospital. Cricothyroidotomy was used successfully in a patient with severe upper airway obstruction as a result of pharyngeal neoplasia. Early intubation-related complications occurred in 52% difficult cases. CONCLUSION: Adherence to a simple algorithm using GEB, ILMA, and cricothyroidotomy solved all difficult intubation cases occurring in a prehospital emergency setting.


Assuntos
Obstrução das Vias Respiratórias/terapia , Algoritmos , Serviços Médicos de Emergência/métodos , Máscaras Laríngeas , Laringoscopia/métodos , Adulto , Idoso , Feminino , França , Humanos , Pessoa de Meia-Idade , Estudos Prospectivos
8.
Cancers (Basel) ; 13(16)2021 Aug 15.
Artigo em Inglês | MEDLINE | ID: mdl-34439263

RESUMO

Photodynamic therapy (PDT) appears to be a promising strategy in biomedical applications. However, the complexity of its parameters prevents wide acceptance. This work presents and characterizes a novel optical device based on knitted light-emitting fabrics and dedicated to in vitro PDT involving low irradiance over a long illumination period. Technical characterization of this device, called CELL-LEF, is performed. A cytotoxic study of 5-ALA-mediated PDT on human cancer cell lines is provided as a proof of concept. The target of delivering an irradiance of 1 mW/cm2 over 750 cm2 is achieved (mean: 0.99 mW/cm2; standard deviation: 0.13 mW/cm2). The device can maintain a stable temperature with the mean thermal distribution of 35.1 °C (min: 30.7 °C; max: 38.4 °C). In vitro outcomes show that 5-ALA PDT using CELL-LEF consistently and effectively induced a decrease in tumor cell viability: Almost all the HepG2 cells died after 80 min of illumination, while less than 60% of U87 cell viability remained. CELL-LEF is suitable for in vitro PDT involving low irradiance over a long illumination period.

9.
J Clin Med ; 9(4)2020 Apr 21.
Artigo em Inglês | MEDLINE | ID: mdl-32326210

RESUMO

Often discovered at an advanced stage, ovarian cancer progresses to peritoneal carcinoma, which corresponds to the invasion of the serosa by multiple tumor implants. The current treatment is based on the combination of chemotherapy and tumor cytoreduction surgery. Despite the progress and standardization of surgical techniques combined with effective chemotherapy, post-treatment recurrences affect more than 60% of women in remission. Photodynamic therapy (PDT) has been particularly indicated for the treatment of superficial lesions on large surfaces and appears to be a relevant candidate for the treatment of microscopic intraperitoneal lesions and non-visible lesions. However, the impact of this therapy on immune cells remains unclear. Hence, the objective of this study is to validate the efficacy of a new photosensitizer [pyropheophorbide a-polyethylene glycol-folic acid (PS)] on human ovarian cancer cells and to assess the impact of the secretome of PDT-treated cells on human peripheral blood mononuclear cells (PBMC). We show that PS, upon illumination, can induce cell death of different ovarian tumor cells. Furthermore, PDT using this new PS seems to favor activation of the immune response by inducing the secretion of effective cytokines and inhibiting the pro-inflammatory and immunosuppressive ones, as well as releasing extracellular vesicles (EVs) prone to activating immune cells. Finally, we show that PDT can activate CD4+ and CD8+ T cells, resulting in a potential immunostimulating process. The results of this pilot study therefore indicate that PS-PDT treatment may not only be effective in rapidly and directly destroying target tumor cells but also promote the activation of an effective immune response; notably, by EVs. These data thus open up good prospects for the treatment of micrometastases of intraperitoneal ovarian carcinosis which are currently inoperable.

10.
J Clin Med ; 9(1)2020 Jan 10.
Artigo em Inglês | MEDLINE | ID: mdl-31936786

RESUMO

To date, pancreatic adenocarcinoma (ADKP) is a devastating disease for which the incidence rate is close to the mortality rate. The survival rate has evolved only 2-5% in 45 years, highlighting the failure of current therapies. Otherwise, the use of photodynamic therapy (PDT), based on the use of an adapted photosensitizer (PS) has already proved its worth and has prompted a growing interest in the field of oncology. We have developed a new photosensitizer (PS-FOL/PS2), protected by a recently published patent (WO2019 016397-A1, 24 January 2019). This photosensitizer is associated with an addressing molecule (folic acid) targeting the folate receptor 1 (FOLR1) with a high affinity. Folate binds to FOLR1, in a specific way, expressed in 100% of ADKP or over-expressed in 30% of cases. The first objective of this study is to evaluate the effectiveness of this PS2-PDT in four ADKP cell lines: Capan-1, Capan-2, MiapaCa-2, and Panc-1. For this purpose, we first evaluated the gene and protein expression of FOLR1 on four ADKP cell lines. Subsequently, we evaluated PS2's efficacy in our cell lines and we assessed the impact of PDT on the secretome of cancer cells and its impact on the immune system. Finally, we evaluate the PDT efficacy on a humanized SCID mouse model of pancreatic cancer. In a very interesting way, we observed a significant increase in the proliferation of activated-human PBMC when cultured with conditioned media of ADKP cancer cells subjected to PDT. Furthermore, to evaluate in vivo the impact of this new PS, we analyzed the tumor growth in a humanized SCID mice model of pancreatic cancer. Four conditions were tested: Untreated, mice (nontreated), mice with PS (PS2), mice subjected to illumination (Light only), and mice subjected to illumination in the presence of PS (PDT). We noticed that the mice subjected to PDT presented a strong decrease in the growth of the tumor over time after illumination. Our investigations have not only suggested that PS2-PDT is an effective therapy in the treatment of PDAC but also that it activates the immune system and could be considered as a real adjuvant for anti-cancer vaccination. Thus, this new study provides new treatment options for patients in a therapeutic impasse and will provide a new arsenal in the fight against PDAC.

11.
Photodiagnosis Photodyn Ther ; 25: 166-176, 2019 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-30543907

RESUMO

BACKGROUND: There is currently no therapy that prevents high-grade glioma recurrence. Thus, these primary brain tumors have unfavorable outcomes. Recently, 5-ALA photodynamic therapy (PDT) has been proposed to delay relapse and is highly expected to have potential synergistic effects with the current standard of care. However, PDT treatment delivery needs to be optimized by evaluating the impact of both the number of fractions and the light power used. OBJECTIVES: Previous studies have reported MRI examination-based outcomes for PDT in glioblastoma. Our study aimed to compare MRI markers across different treatment schemes that use interstitial PDT in high-grade glioma in a preclinical model. MATERIALS AND METHODS: Forty-eight "nude" rats were grafted with human U87 cells into the right putamen and subsequently submitted to interstitial PDT. The rats were randomized into six groups, including two different sham groups and four different treated groups (5 fractions at 5 mW or 30 mW and 2 fractions at 5 mW or 30 mW). After photosensitizer (PS) precursor (5-ALA) intake, an optical fiber was introduced into the tumor. Treatment effects were assessed with early high-field MRI to acquire T1 and T2 diffusion and perfusion images. RESULTS: There was no difference in the variation of the diffusion coefficient among the six groups (p = 0.0549, Kruskal-Wallis test). However, a significant difference was identified among the six groups in terms of variation in perfusion (p = 0.048, Kruskal-Wallis test), supporting a lesional effect in the treated groups. Additionally, the sham groups had significantly smaller edema volumes than were observed in the treated groups. Moreover, the 5-fraction group treated with 30 mW was associated with edema volumes that were significantly greater than those in the 5-fraction group treated with 5 mW (p = 0.019). CONCLUSION: Based on observations of MRI data and considering treatment effects, the 5-fraction group treated at 5 mW was not significantly different from the other treated groups in terms of cell deaths, characterized by diffusion imaging, or necrosis level. However, the significantly lower level of edema observed in this group indicated that this treatment scheme had limited toxicity.


Assuntos
Ácido Aminolevulínico/farmacologia , Neoplasias Encefálicas/tratamento farmacológico , Glioma/tratamento farmacológico , Fotoquimioterapia/métodos , Fármacos Fotossensibilizantes/farmacologia , Ácido Aminolevulínico/administração & dosagem , Animais , Biomarcadores Tumorais , Neoplasias Encefálicas/diagnóstico por imagem , Linhagem Celular Tumoral , Glioma/diagnóstico por imagem , Humanos , Lasers Semicondutores/uso terapêutico , Imageamento por Ressonância Magnética , Fármacos Fotossensibilizantes/administração & dosagem , Distribuição Aleatória , Ratos , Ratos Nus
12.
Ann Emerg Med ; 50(3): 258-63, 2007 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-17583382

RESUMO

STUDY OBJECTIVE: The objective of this study was to compare, in the emergency out-of-hospital environment, intubation success rates during the first laryngoscopy for 2 laryngoscope blade types: a metallic reusable and a plastic single-use. METHODS: An observational before-and-after study was conducted during 2 1-year periods. Adult patients were intubated by emergency physicians, anesthesiologists, or anesthesia nurses in the out-of-hospital setting with metallic reusable (first period) or a plastic disposable (second period) Macintosh 3 or 4 laryngoscope blades. Immediately after intubation, data were collected on success rate of intubation at the first attempt, intubation difficulty score, quality of laryngeal visualization, and the need for alternative airway techniques. To compare the 2 periods of the study, Wilcoxon's test was used for quantitative variables, and the chi2 or Fisher's exact test was used for qualitative variables. RESULTS: Patients intubated with a metallic blade (594/1,177; 50.5%) and with a plastic blade (583/1,177; 49.5%) were included in the study. The first-attempt intubation success rate was higher in the metallic blade group (497/594, 84%) than in the single-use group (76%); difference 7% (95% confidence interval [CI] 3% to 12%) (P<.002). The incidence of difficult intubation, defined by an intubation difficulty score greater than 5, was lower (6% [95% CI 4% to 8%] versus 15% [95% CI 12% to 18%]) when metallic blades were used. A good laryngeal view (Cormack and Lehane classes I and II) was more frequently observed with metallic blade use (83% [95% CI 80% to 86%] versus 67% [95% CI 64% to 70%]). Alternative airway techniques such as the use of a Gum elastic bougie or an intubating laryngeal mask airway were more frequently used in the plastic blade period (12% [95% CI 10% to 14%] versus 4% [95% CI 2% to 6%]). CONCLUSION: In out-of-hospital emergency care, the use of a plastic disposable laryngoscope blade decreased the success rate of tracheal intubation at the first attempt performed by emergency care providers.


Assuntos
Intubação Intratraqueal/instrumentação , Laringoscópios , Adulto , Distribuição de Qui-Quadrado , Equipamentos Descartáveis , Desenho de Equipamento , Humanos , Plásticos , Estudos Prospectivos , Estatísticas não Paramétricas
13.
Photodiagnosis Photodyn Ther ; 13: 218-224, 2016 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-26213327

RESUMO

OBJECTIVE: Photodynamic therapy (PDT) has become a well-established modality for the treatment of many cancers. Photodynamic eradication of tumor cells depends on the presence of a photosensitizer, oxygen and light. However, oxygen depletion during PDT is a well known problem. Modulation of light delivery could address this issue by counteracting tumor hypoxia, thereby improving tumor cell killing. This preclinical study was designed to validate an animal model incorporating 5-aminolaevulinic acid (5-ALA)-PDT using U87 glioblastoma cells. We aimed to evaluate the effects of light modulation for inducing specific tumoral lesions in this model (i.e., necrosis or apoptosis). MATERIALS AND METHODS: U87 glioblastoma cells were stereotactically engrafted into the brains of male fox1 rnu/rnu rats. Light delivery was studied after 5-ALA injection (100 mg/kg i.p.). 26J of 635 nm light was interstitially delivered to U87 tumor-bearing rats at a radiant power of either 30 mW (high fluence rate) or 4.8 mW (low fluence rate). In each group, half of the population received illumination in 2 fractions with a refractory interval of 120 s, whereas the other half received continuous illumination. RESULTS: Twenty-two animals received 5-ALA-PDT, and the level of necrosis was scored. In the high-fluence-rate group, we observed a greater degree of tumor necrosis in rats receiving fractionated delivery than in rats receiving continuous illumination. Similar differences were not observed in the low-fluence-rate group, which exhibited only sparse necrosis. Higher morbidity and mortality rates were observed in the high-fluence-rate group. CONCLUSION: We have developed a reproducible and reliable rodent model for interstitial 5-ALA PDT. We found that the effects of 5-ALA-PDT are dependent on light delivery conditions. Although the low-fluence-rate treatment was better tolerated, 5-ALA-PDT induced more necrosis using fractionated delivery at a high fluence rate. These results require confirmation with further studies involving larger populations and additional fractionation schemes.


Assuntos
Ácido Aminolevulínico/administração & dosagem , Neoplasias Encefálicas/tratamento farmacológico , Neoplasias Encefálicas/patologia , Glioblastoma/tratamento farmacológico , Glioblastoma/patologia , Fotoquimioterapia/métodos , Animais , Linhagem Celular Tumoral , Fracionamento da Dose de Radiação , Relação Dose-Resposta a Droga , Relação Dose-Resposta à Radiação , Avaliação Pré-Clínica de Medicamentos/métodos , Estudos de Viabilidade , Humanos , Fármacos Fotossensibilizantes/administração & dosagem , Projetos Piloto , Ratos , Ratos Nus , Taxa de Sobrevida , Resultado do Tratamento
14.
Adv Urol ; 2012: 589160, 2012.
Artigo em Inglês | MEDLINE | ID: mdl-22666240

RESUMO

Current challenges and innovations in prostate cancer management concern the development of focal therapies that allow the treatment of only the cancer areas sparing the rest of the gland to minimize the potential morbidity. Among these techniques, focal laser ablation (FLA) appears as a potential candidate to reach the goal of focusing energy delivery on the identified targets. The aim of this study is to perform an up-to-date review of this new therapeutic modality. Relevant literature was identified using MEDLINE database with no language restrictions (entries: focal therapy, laser interstitial thermotherapy, prostate cancer, FLA) and by cross-referencing from previously identified studies. Precision, real-time monitoring, MRI compatibility, and low cost of integrated system are principal advantages of FLA. Feasibility and safety of this technique have been reported in phase I assays. FLA might eventually prove to be a middle ground between active surveillance and radical treatment. In conclusion, FLA may have found a role in the management of prostate cancer. However, further trials are required to demonstrate the oncologic effectiveness in the long term.

16.
Acad Emerg Med ; 13(8): 828-34, 2006 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-16807397

RESUMO

OBJECTIVES: The rate of difficult intubation in prehospital emergency medicine varies greatly among studies already published and depends on several factors. The authors' objective was to determine the rate of difficult intubations and to determine factors associated with prehospital difficult airways when a standard protocol for sedation and intubation was applied. METHODS: This 30-month clinical, observational, prospective study was performed in a suburb of Paris, France (Val de Marne, population 1,300,000) by a prehospital emergency medical unit. Airway management for patients who needed tracheal intubation was standardized. The pharmacological procedure recommended rapid sequence intubation for patients with spontaneous cardiac activity. In cases of difficult, laryngoscopy-assisted intubation, a predefined algorithm was proposed. The Intubation Difficulty Score (IDS) was calculated for all patients requiring tracheal intubation, and factors associated with difficult intubation, defined by IDS of >5, were identified by using multivariate statistical analysis. RESULTS: During the study period, 1,442 patients were included; 640 (44%) were in cardiorespiratory arrest, and 802 had a spontaneous cardiac activity. Deviation from the pharmacological and airway management procedures occurred in 1% of cases. When the predefined difficult airway management algorithm was followed, failure to intubate was encountered twice (0.1%). One hundred six (7.4%) patients had an IDS of >5, and 60 (4.1%) required first (n = 56) then second (n = 4) alternative techniques for tracheal intubation. Semirigid leaders allowed tracheal access in 93% of difficult-intubation patients. One patient required a prehospital cricothyroidotomy. Factors associated with difficult intubation were the following: a history of ear, nose, or throat neoplasia or surgery; obesity; facial trauma; the operator's status; and the operator's position. CONCLUSIONS: If prehospital medical airway management is standardized and performed by trained operators, failure to intubate is rare (0.1%), and the incidence of difficult tracheal intubation is 7.4%, independent of cardiorespiratory status.


Assuntos
Obstrução das Vias Respiratórias/terapia , Protocolos Clínicos , Serviços Médicos de Emergência/estatística & dados numéricos , Serviços Médicos de Emergência/normas , Intubação Intratraqueal/estatística & dados numéricos , Intubação Intratraqueal/normas , Obstrução das Vias Respiratórias/epidemiologia , Serviços Médicos de Emergência/métodos , Feminino , França/epidemiologia , Humanos , Hipnóticos e Sedativos/uso terapêutico , Incidência , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Estudos Prospectivos , Fatores de Risco , Falha de Tratamento
17.
Am J Emerg Med ; 23(4): 552-5, 2005 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-16032630

RESUMO

The objective of this study was to assess effectiveness of gum elastic bougie (GEB) in case of difficult intubation occurring in the prehospital settings. After manikin training to GEB handling, physicians were recommended to use GEB as first alternative technique in case of difficult intubation. Intubating conditions and details of patients requiring GEB-assisted laryngoscopy were recorded over 30 months. Among the 1442 extrahospital intubations performed, 41 patients (3%) required GEB. Gum elastic bougie allowed successful intubation in 33 cases (78%) and 8 patients sustained a second alternative technique. One patient was never intubated, another 1 required rescue cricothyroidotomy. Twenty-four (60%) GEB patients had associated factors for difficult intubation such as reduced or limited cervical spine mobility, morbid obesity, cervicofacial trauma, and ears, nose, and throat neoplasia. The success rate of GEB was 75% and 94%, respectively, depending on whether associated factors for difficult intubation are present or not. No adverse events associated to GEB use were noted.


Assuntos
Obstrução das Vias Respiratórias/terapia , Serviços Médicos de Emergência/métodos , Intubação Intratraqueal/instrumentação , Serviços Médicos de Emergência/estatística & dados numéricos , Falha de Equipamento , Segurança de Equipamentos , Feminino , França , Humanos , Intubação Intratraqueal/métodos , Intubação Intratraqueal/estatística & dados numéricos , Masculino , Pessoa de Meia-Idade , Resultado do Tratamento
18.
Anesthesiology ; 102(6): 1106-9; discussion 5A, 2005 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-15915021

RESUMO

BACKGROUND: The intubating laryngeal mask airway (ILMA) was designed using the characteristics of healthy-weight subjects but was shown to be an effective airway device in morbidly obese patients. The authors compared airway management quality in morbidly obese and lean patients with use of the ILMA. METHODS: Fifty morbidly obese and 50 lean patients (mean body mass indexes, 42 and 27 kg/m, respectively) were enrolled in this prospective study. After induction of general anesthesia, characteristics of airway management were judged on safety and efficiency parameters, including success rate at ventilation and intubation and airway management quality criteria, such as the number of patients who required adjustment maneuvers, the number of failed tracheal intubation attempts, the total duration of airway management, and an overall difficulty visual analog scale score. RESULTS: The ILMA was successfully inserted and adequate ventilation through the ILMA was achieved in all 100 patients. The success rates of tracheal intubation through the ILMA were similar in obese and lean patients (96% and 94%, respectively). The numbers of failed blind tracheal access attempts and patients who required airway-adjustment maneuvers were significantly reduced in obese patients as compared with lean patients. Four obese patients experienced transient episodes of oxygen desaturation (oxygen saturation < 90%) before adequate bag ventilation was established with the ILMA. CONCLUSION: The authors confirmed that the ILMA was an efficient airway device for airway management of both lean and obese patients. In the conditions of this study, the authors observed that airway management with the ILMA was simpler in obese patients as compared with lean patients.


Assuntos
Máscaras Laríngeas/estatística & dados numéricos , Máscaras Laríngeas/normas , Obesidade Mórbida/epidemiologia , Magreza/epidemiologia , Adulto , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos
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