RESUMEN

Inhibitors of the hedgehog pathway are effective in patients with basal cell carcinoma and a subgroup of patients with medulloblastoma with active hedgehog signaling. Despite preclinical work suggesting otherwise, clinical trials in solid tumors of epithelial origin have not shown added benefit with these drugs. Here, we review the preclinical and clinical data of hedgehog pathway inhibition in the most common histologic types of lung cancer. We focus on highlighting areas of uncertainty, where further research might define a niche for hedgehog pathway inhibition in patients with lung cancer.

Asunto(s)

Antineoplásicos/uso terapéutico , Proteínas Hedgehog/metabolismo , Neoplasias Pulmonares/metabolismo , Animales , Antineoplásicos/farmacología , Carcinoma Basocelular/tratamiento farmacológico , Ensayos Clínicos como Asunto , Evaluación Preclínica de Medicamentos , Proteínas Hedgehog/antagonistas & inhibidores , Humanos , Neoplasias Pulmonares/tratamiento farmacológico , Meduloblastoma/tratamiento farmacológico , Transducción de Señal

RESUMEN

In the present work, the thermal processing of table olives in brine in a stationary metal can was studied through computational fluid dynamics (CFD). The flow patterns of the brine and the temperature evolution in the olives and brine during the heating and the cooling cycles of the process were calculated using the CFD code. Experimental temperature measurements at 3 points (2 inside model olive particles and 1 at a point in the brine) in a can (with dimensions of 75 mm × 105 mm) filled with 48 olives in 4% (w/v) brine, initially held at 20 °C, heated in water at 100 °C for 10 min, and thereafter cooled in water at about 20 °C for 10 min, validated model predictions. The distribution of temperature and F-values and the location of the slowest heating zone and the critical point within the product, as far as microbial destruction is concerned, were assessed for several cases. For the cases studied, the critical point was located at the interior of the olives at the 2nd, or between the 1st and the 2nd olive row from the bottom of the container, the exact location being affected by olive size, olive arrangement, and geometry of the container.

Asunto(s)

Manipulación de Alimentos/métodos , Hidrodinámica , Olea/química , Temperatura , Biología Computacional , Microbiología de Alimentos , Modelos Teóricos , Reproducibilidad de los Resultados , Sales (Química)/análisis , Programas Informáticos

RESUMEN

BACKGROUND: We sought to determine biomarker expression differences in head and neck squamous cell cancers (HNSCCs) based on p16/human papillomavirus (HPV) classification. In addition, our aim was to explore how expression of biomarkers is modulated after E6/E7 repression in HPV16⁺ oropharyngeal cancer cells. METHODS: HPV16⁺ and HPV⁻ HNSCC cells were infected with retroviruses expressing short hairpin RNA targeting HPV16 E6/E7. Components of the epidermal growth factor receptor (EGFR) pathway before and after E6/E7 gene silencing were analyzed by immunoblotting and qRT-PCR. Protein expression of 13 biomarkers was analyzed using AQUA on a tissue microarray (TMA). The HPV16 status was determined using HPV16 in situ hybridization (ISH). RESULTS: In HPV16⁺ cells, E6/E7 silencing was associated with PTEN upregulation and reduction of phosphorylated EGFR. Tumors were classified into four categories based on the HPV and p16 status. HPV⁺/p16⁺ tumors expressed significantly higher levels of E-cadherin (P = 0.003), PTEN (P = 0.004), lower levels of PI3Kp110 and ß-catenin (P = 0.07). There was a significant difference in overall survival (OS, P = 0.016) among the four subsets. The median OS was 24.83 months for p16⁻/HPV⁻ patients, 11.63 for p16⁻/HPV⁺ patients and was not reached for p16⁺/HPV⁻ and p16⁺/HPV⁺ groups. CONCLUSIONS: Aberrant EGFR signaling contributes to malignant conversion of HPV16⁺ HNSCC cells. These results validate ß-catenin as a distinct biomarker in HPV⁺/p16⁺ HNSCC. Wnt signaling inhibitors merit exploration in HPV⁺/p16⁺ HNSCC.

Asunto(s)

Carcinoma de Células Escamosas/metabolismo , Receptores ErbB/metabolismo , Neoplasias de Cabeza y Cuello/metabolismo , Proteínas de Neoplasias/metabolismo , Neoplasias Orofaríngeas/metabolismo , beta Catenina/metabolismo , Biomarcadores de Tumor/metabolismo , Carcinoma de Células Escamosas/genética , Carcinoma de Células Escamosas/virología , Línea Celular Tumoral , Inhibidor p16 de la Quinasa Dependiente de Ciclina , Receptores ErbB/genética , Femenino , Neoplasias de Cabeza y Cuello/genética , Neoplasias de Cabeza y Cuello/virología , Humanos , Masculino , Proteínas Oncogénicas Virales/genética , Proteínas Oncogénicas Virales/metabolismo , Neoplasias Orofaríngeas/genética , Neoplasias Orofaríngeas/virología , Fosfohidrolasa PTEN/biosíntesis , Proteínas E7 de Papillomavirus/genética , Proteínas E7 de Papillomavirus/metabolismo , Infecciones por Papillomavirus/complicaciones , Infecciones por Papillomavirus/genética , Infecciones por Papillomavirus/virología , Fosforilación , Interferencia de ARN , ARN Interferente Pequeño , Proteínas Represoras/genética , Proteínas Represoras/metabolismo , Carcinoma de Células Escamosas de Cabeza y Cuello , Proteína p53 Supresora de Tumor/metabolismo , Vía de Señalización Wnt

Asunto(s)

Carcinoma Basocelular/epidemiología , Neoplasias Cutáneas/epidemiología , Adolescente , Adulto , Distribución por Edad , Anciano , Anciano de 80 o más Años , Niño , Preescolar , Femenino , Grecia/epidemiología , Humanos , Lactante , Masculino , Persona de Mediana Edad , Caracteres Sexuales

Asunto(s)

Enfermedades de la Piel/epidemiología , Adolescente , Adulto , Factores de Edad , Anciano , Anciano de 80 o más Años , Niño , Preescolar , Estudios Transversales , Femenino , Humanos , Lactante , Recién Nacido , Masculino , Persona de Mediana Edad

RESUMEN

AIMS: In this study, we have investigated the biochemical behaviour of Aspergillus sp. (five strains) and Penicillium expansum (one strain) fungi cultivated on waste cooking olive oil. The production of lipid-rich biomass was the main target of the work. In parallel, the biosynthesis of other extracellular metabolites (organic acids) and enzyme (lipase) and the substrate fatty acid specificity of the strains were studied. METHODS AND RESULTS: Carbon-limited cultures were performed on waste oil, added in the growth medium at 15g l(-1) , and high biomass quantities were produced (up to c.18g l(-1) , conversion yield of c. 1·0 g of dry biomass formed per g of fat consumed or higher). Cellular lipids were accumulated in notable quantities in almost all cultures. Aspergillus sp. ATHUM 3482 accumulated lipid up to 64·0% (w/w) in dry fungal mass. In parallel, extracellular lipase activity was quantified, and it was revealed to be strain and fermentation time dependent, with a maximum quantity of 645 U ml(-1) being obtained by Aspergillus niger NRRL 363. Storage lipid content significantly decreased at the stationary growth phase. Some differences in the fatty acid composition of both cellular and residual lipids when compared with the initial substrate fat used were observed; in various cases, cellular lipids more saturated and enriched with arachidic acid were produced. Aspergillus strains produced oxalic acid up to 5·0 g l(-1) . CONCLUSIONS: Aspergillus and Penicillium strains are able to convert waste cooking olive oil into high-added-value products. SIGNIFICANCE AND IMPACT OF THE STUDY: Increasing fatty wastes amounts are annually produced. The current study provided an alternative way of biovalourization of these materials, by using them as substrates, to produce added-value compounds.

Asunto(s)

Aspergillus/metabolismo , Microbiología Industrial/métodos , Lípidos/biosíntesis , Penicillium/metabolismo , Aceites de Plantas/química , Eliminación de Residuos Líquidos/métodos , Aspergillus/crecimiento & desarrollo , Biomasa , Reactores Biológicos , Biotecnología/métodos , Culinaria , Medios de Cultivo , Fermentación , Lipasa/metabolismo , Aceite de Oliva , Penicillium/crecimiento & desarrollo , Especificidad por Sustrato

RESUMEN

The electrochemical oxidation of olive mill wastewater (OMW) and model compounds over a Ti/IrO(2) anode was studied by means of cyclic voltammetry and bulk electrolysis. Experiments were conducted at 1300 mg/L initial COD, 0-1.23V vs SHE and 1.4-1.54V vs SHE potential windows, 50 mA/cm(2) current density, 0-25 mM NaCl, 60-80 degrees C temperature and acidic conditions. The reactivity of model compounds decreases in the order phenol approximately p-coumaric acid>cinnamic acid>caffeic acid. Partial and total oxidation reactions occur with the overall rate following zero-order kinetics with respect to COD and increasing with temperature. Oxidation of OMW at 43 Ah/L, 80 degrees C and in the presence of 5mM NaCl leads to complete color and phenols removal, elimination of ecotoxicity but moderate (30%) COD reduction. Similar performance can be achieved at 6 Ah/L in the presence of 15 mM NaCl. In the absence of salt, the respective color and phenols removal (at 6 Ah/L) is less than 10%. Excessive salinity (25 mM), although does not change color, phenols and COD removal, has an adverse effect on ecotoxicity.

Asunto(s)

Técnicas Electroquímicas/métodos , Residuos Industriales/prevención & control , Olea , Contaminantes Químicos del Agua/química , Técnicas Electroquímicas/instrumentación , Electrodos , Restauración y Remediación Ambiental/métodos , Iridio , Oxidación-Reducción , Titanio

RESUMEN

The photochemical persistence of quinalphos, one of the most widely used organophosphorous insecticides, was investigated in a variety of environmental matrices such as natural waters and soils of different composition. Simulated solar irradiation was obtained using a xenon arc lamp (Suntest CPS+ apparatus) giving an irradiation intensity of 750 W m(-2) equivalent to a light dose per hour of irradiation of 2,700 kJ m(-2). The phototransformation rates were determined using solid-phase microextraction (SPME) and ultrasonic extraction (USE) coupled to GC-FTD, while the identification of photoproducts was carried out by GC-MS. In water samples, the degradation kinetics followed a pseudo-first-order reaction and photolysis half-lives ranged between 11.6 and 19.0 h depending on the constitution of the irradiated media. Dissolved organic matter (DOM) has a predominant retarding effect, while nitrate ions accelerated the photodegradation kinetics. In soil samples, the degradation kinetics was monitored on 1mm soil layer prepared on glass TLC plates. The kinetic behaviour of quinalphos was complex and characterized by a double step photoreaction, fast in the first 4h of irradiation followed by a slow degradation rate up to 64 h. The photolysis half-life of quinalphos was shorter in sandy soil compared to the rest of the soil samples, varying between 16.9 and 47.5 h, and showing a strong dependence on the composition of the irradiated media. Among the transformation products formed mainly through photohydrolysis and photoisomerization processes, some photoproduct structures were proposed according to their mass spectral information.

Asunto(s)

Agua Dulce/análisis , Modelos Químicos , Compuestos Organotiofosforados/análisis , Contaminantes del Suelo/análisis , Luz Solar , Contaminantes Químicos del Agua/análisis , Cromatografía de Gases , Cinética , Espectrometría de Masas , Compuestos Organotiofosforados/efectos de la radiación , Fotólisis , Contaminantes del Suelo/efectos de la radiación , Contaminantes Químicos del Agua/efectos de la radiación

RESUMEN

Waterbirds are particularly subject to accumulation of persistent organic pollutants (POPs) that have been shown to constitute a major hazard for this group of birds. Liver and fat tissue from ten species belonging to the orders Ciconiformes (Ardeidae, Ciconiidae, Phoenicopteridae) and Pelicaniformes (Pelecanidae, Phalacrocoracidae) were used as bioindicators in order to assess environmental pollution by POPs (HCHs, DDTs, cyclodienes, PCBs) in Greek wetlands. To our knowledge, this is the first study on POPs in livers of water birds in Greece and Eastern Mediterranean area. The DDTs consisted mainly of p,p'-DDE with percentages over 60% in the great majority of the samples. The highest summation SigmaDDT concentrations were measured in the liver and subcutaneous fat of Phoenicopterus rubber and in Ardea purpurea liver (15565, 24706 and 10406 ng g(-1) wet weight, respectively). Low concentrations of cyclodienes (Cycls) and HCHs were detected occasionally and the contamination pattern of OCPs in most species of waterbirds followed the order summation SigmaDDTs> summation SigmaCycls> summation SigmaHCHs. Individual values of total PCBs reached the levels of 4468 and 3252 ng g(-1) wet weight, for Nycticorax nycticorax and Egretta garzetta samples respectively. Some of the recorded differences in organochlorine concentrations could be due to different causes of death, with a subsequent effect on body lipid levels. Organochlorine pesticides and PCBs residues were lower than those commonly associated with mortality and reduced reproductive success in most species. However, low level exposure to these contaminants may constitute one of the many stressors that in combination could adversely affect bird populations.

Asunto(s)

Tejido Adiposo/química , Aves/metabolismo , Hidrocarburos Clorados/análisis , Hígado/química , Contaminantes Químicos del Agua/análisis , Animales , Dieta , Monitoreo del Ambiente , Femenino , Peces , Grecia , Hidrocarburos Clorados/metabolismo , Masculino , Contaminantes Químicos del Agua/metabolismo

Asunto(s)

Huevos/análisis , Compuestos de Metilmercurio/análisis , Animales , Pollos , Femenino , Compuestos de Metilmercurio/farmacocinética

Asunto(s)

Huevos/análisis , Contaminación de Alimentos/análisis , Carne/análisis , Compuestos de Metilmercurio/análisis , Animales , Pollos , Cromatografía de Gases , Femenino , Hígado/análisis