Carcinoma no microcítico de pulmón localmente avanzado tratado con quimioradioterapia en el Hospital Universitario Marqués de Valdecilla (HUMV) en 2013 y 2014: Resultados de toxicidad y supervivencia.

RESUMEN: El carcinoma no microcítico de pulmón es una neoplasia de alta incidencia y mortalidad en el mundo y en nuestro entorno. En pacientes con estadio localmente avanzado al diagnóstico, el tratamiento consiste en quimioradioterapia concomitante con intención radical. Analizamos para el presente trabajo de manera retrospectiva a los 66 pacientes con este diagnóstico que recibieron quimioradioterapia concomitante o radioterapia exclusiva en el Hospital Universitario Marqués de Valdecilla durante los años 2013 y 2014. Observamos una baja incidencia de toxicidad aguda y crónica. Tras un seguimiento mediano de 17 meses (rango tres a 41 meses) reportamos una supervivencia global al año de 53-64% y a los dos años de 35-37%, y una supervivencia media de 16.5 - 19.4 meses. En comparación con datos de supervivencia de estudios internacionales nuestros resultados son equiparables.ABSTRACT: Non small cell lung carcinoma is a neoplasm of high incidence and mortality both worldwide and in our region. In patients with locally advanced stage at diagnosis, treatment consists of concomitant chemoradiotherapy with curative intention. We retrospectively analyzed the 66 patients with this diagnosis who received concomitant chemoradiotherapy or radiotherapy alone at the University Hospital of Marqués de Valdecilla in the years 2013 and 2014. We observed a low incidence of acute and chronic toxicity. After a median follow-up of 17 months (range three to 41 months) we report overall survival of 53-64% at one year and 35-37% at two years, and median survival of 16.5 - 19.4 months. In comparison with survival data from international studies our results are equivalent

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Assessment of a New ROS1 Immunohistochemistry Clone (SP384) for the Identification of ROS1 Rearrangements in Patients with Non–Small Cell Lung Carcinoma: the ROSING Study

Introduction: The ROS1 gene rearrangement has become an important biomarker in NSCLC. The College of American Pathologists/International Association for the Study of Lung Cancer/Association for Molecular Pathology testing guidelines support the use of ROS1 immunohistochemistry (IHC) as a screening test, followed by confirmation with fluorescence in situ hybridization (FISH) or a molecular test in all positive results. We have evaluated a novel anti-ROS1 IHC antibody (SP384) in a large multicenter series to obtain real-world data. Methods: A total of 43 ROS1 FISH-positive and 193 ROS1 FISH-negative NSCLC samples were studied. All specimens were screened by using two antibodies (clone D4D6 from Cell Signaling Technology and clone SP384 from Ventana Medical Systems), and the different interpretation criteria were compared with break-apart FISH (Vysis). FISH-positive samples were also analyzed with next-generation sequencing (Oncomine Dx Target Test Panel, Thermo Fisher Scientific). Results: An H-score of 150 or higher or the presence of at least 70% of tumor cells with an intensity of staining of 2+ or higher by the SP384 clone was the optimal cutoff value (both with 93% sensitivity and 100% specificity). The D4D6 clone showed similar results, with an H-score of at least 100 (91% sensitivity and 100% specificity). ROS1 expression in normal lung was more frequent with use of the SP384 clone (p < 0.0001). The ezrin gene (EZR)-ROS1 variant was associated with membranous staining and an isolated green signal FISH pattern (p = 0.001 and p = 0.017, respectively). Conclusions: The new SP384 ROS1 IHC clone showed excellent sensitivity without compromising specificity, so it is another excellent analytical option for the proposed testing algorithm

CIBERER : Spanish national network for research on rare diseases: A highly productive collaborative initiative

Altres ajuts: Instituto de Salud Carlos III (ISCIII); Ministerio de Ciencia e Innovación.CIBER (Center for Biomedical Network Research; Centro de Investigación Biomédica En Red) is a public national consortium created in 2006 under the umbrella of the Spanish National Institute of Health Carlos III (ISCIII). This innovative research structure comprises 11 different specific areas dedicated to the main public health priorities in the National Health System. CIBERER, the thematic area of CIBER focused on rare diseases (RDs) currently consists of 75 research groups belonging to universities, research centers, and hospitals of the entire country. CIBERER's mission is to be a center prioritizing and favoring collaboration and cooperation between biomedical and clinical research groups, with special emphasis on the aspects of genetic, molecular, biochemical, and cellular research of RDs. This research is the basis for providing new tools for the diagnosis and therapy of low-prevalence diseases, in line with the International Rare Diseases Research Consortium (IRDiRC) objectives, thus favoring translational research between the scientific environment of the laboratory and the clinical setting of health centers. In this article, we intend to review CIBERER's 15-year journey and summarize the main results obtained in terms of internationalization, scientific production, contributions toward the discovery of new therapies and novel genes associated to diseases, cooperation with patients' associations and many other topics related to RD research

Effect of a bacteriocin-producing lactic culture and high pressure treatment on the colour of Hispánico cheese

The effect of the addition of a bacteriocin-producing (BP) culture to milk, individually or combined with high pressure (HP) treatment (400 MPa, 5 min, 10°C) applied on day 15 of ripening, on the colour of Hispánico cheese was investigated. Objective colour parameters L* (lightness), a* (green to red), b* (blue to yellow), colour saturation (C) and hue angle (h) of freshly cut samples were determined using a spectrophotometer, after 15, 25 and 50 d of ripening. Addition of BP culture increased L*, b* and C values of cheeses, moving their hue angle towards the yellow direction. HP treatment of cheese made without BP culture decreased cheese L* values, and increased b* and C values. On the other hand, HP treatment of cheese made with BP culture decreased L*, and diminished b* and C values up to 25 d of ripening. In general, colour changes caused by BP culture addition or HP treatment could be related with the colour of older cheeses. Ripening time increased b* and C values, and shifted hue angle of all cheeses but the control cheese to the yellow direction. Short exposures (15 min) of cheese samples to room air/light conditions generally reduced L* and a* values, and increased b* and C values

The influence of some manufacturing and ripening parameters on the colour of ewes' milk cheese

Objective colour of semi-hard ewes' milk cheeses was assessed using a spectrophotometer after 30, 60 and 90 d of ripening. L*, a* and b* (CIE-LAB colour space) parameters of freshly cut samples were determined, and colour saturation (C) and hue angle (h) calculated. Colour of ewes' milk cheeses was light and slightly yellow-greenish. Pasteurization of milk resulted in higher L* (lightness), a* (greenness) and b* (yellowness) values of cheeses, intensifying their colour without changing markedly their tone with respect to that of raw milk cheeses. In general, as cheeses aged their L* value decreased, what can be related to the increase in their dry matter content. Ripening time especially affected pasteurized milk cheeses, which showed increases in b* values and colour saturation and whose hue angle shifted to yellow. Addition of a bacteriocin-producing (BP) adjunct culture diminished L* and a* values of raw milk cheeses, moving the hue angle towards the greenish direction. Pasteurized milk cheeses were not affected by BP addition. When freshly cut samples were exposed to air/light for 15 min, they showed lower L* and a* values, and higher b* values, increasing colour saturation but not affecting its tone, probably due to dehydration of cheese surface

Characteristics of Manchego cheese made from pasteurized ewes' milk inoculated with a bacteriocin-producing adjunct culture

The potential of using a bacteriocin-producing Lactococcus lactis strain to induce lysis of a Streptococcus thenmophilus culture, and to accelerate proteolysis and flavour formation in Manchego cheese, has been investigated. Two vats of cheese were manufactured from pasteurized ewes' milk in duplicate trials. Milk in the experimental vat was inoculated with L lactis subsp. lactis 415, a nisin Z and lacticin 481 producer. L lactis subsp. lactis INIA 415-2, a bacteriocinnonproducing mutant, was used as mesophilic starter in both vats. Cheeses were ripened at 12°C and 85% RH for 90 days. Microbiological, physicochemical, enzymatic, proteolytic, textural and sensory characteristics of cheeses were assessed S. thermophilus counts were lowered by the bacteriocin, aminopeptidase activity was slightly increased during early ripening, and proteolysis (estimated by the o-phthaldialdehyde method) was significantly higher throughout ripening. In spite of the enhanced proteolysis, textural and sensory characteristics of Manchego cheese were not significantly influenced by milk inoculation with the bacteriocin producer

Effect of reuterin-producing Lactobacillus reuteri coupled with glycerol on the volatile fraction, odour and aroma of semi-hard ewe milk cheese

The effect of the biopreservation system formed by Lactobacillus reuteri INIA P572, a reuterin-producing strain, and glycerol (required for reuterin production), on the volatile fraction, aroma and odour of industrial sized semi-hard ewe milk cheese (Castellano type) was investigated over a 3-month ripening period. The volatile compounds were extracted and analyzed by SPME-GC-MS and cheese odour and aroma profiles were studied by descriptive sensory analysis. Control cheese was made only with a mesophilic starter and experimental cheeses with L. reuteri were made with and without glycerol. The addition of L. reuteri INIA P572 to milk enhanced the formation of six volatile compounds. Despite the changes in the volatile compounds profile, the use of L. reuteri INIA P572 did not noticeably affect the sensory characteristics of cheese. On the other hand, the addition of L. reuteri INIA P572 coupled with 30 mM glycerol enhanced the formation of twelve volatile compounds, but decreased the formation of five ones. The use of the biopreservation system did not affect overall odour and aroma quality of cheese although it resulted in a significant decrease of the odour intensity scores. In addition, this cheese received significant higher scores for "cheesy" aroma and significant lower scores for the aroma attributes "milky", "caramel" and "yogurt-like". The first two axes of a principal component analysis (PCA) performed for selected volatile compounds and sensory characteristics, accounting for 75% of the variability between cheeses, separated cheeses made with L. reuteri INIA P572 and glycerol from the rest of cheeses, and also differentiated control cheese from cheeses made with L. reuteri INIA P572 from day 60 onward. Our results showed that the reuterin-producing L. reuteri INIA P572 strain, when coupled with glycerol, may be a suitable biopreservation system to use in cheese without affecting odour and aroma quality. © 2016 Elsevier B.V

Effect of milk inoculation with bacteriocin-producing lactic acid bacteria on a Lactobacillus helveticus adjunct cheese culture

The effect of eight strains of lactic acid bacteria (two strains of Enterococcus, one strain of Lactobacillus, and five strains of Lactococcus, which produce enterocin AS-48, enterocin 607, nisin A, nisin Z, plantaricin 684, lacticin 481, or nisin Z plus lacticin 481) on acid production and proteolytic activity of Lactobacillus helveticus LH 92 (a highly peptidolytic strain used as an adjunct in cheese making) was evaluated in mixed cultures in milk. Acid production by mixed cultures depended on the sensitivity of L. helveticus LH 92 to the different bacteriocins and on the acidification rates of bacteriocin-producing strains. Proteolysis values of mixed cultures were, in all cases, lower than those of L. helveticus LH 92 single culture (control). Cell-free aminopeptidase activity values after 9 h of incubation did not increase in the presence of enterocin producers or the nisin A producer, whereas in the presence of the nisin Z producer, cell-free aminopeptidase activity was, at most, 3.7-fold greater than the control value. In mixed cultures with the plantaricin producer, a progressive lysis of L. helveticus LH 92 took place, with cell-free aminopeptidase activity values after 9 h being, at most, 10.5-fold greater than the control value. The highest cell-free aminopeptidase activity values after 9 h were recorded in the presence of lacticin 481 producers, with the values being, at most, 25.1-fold greater than the control value. L. helveticus LH 92 was extremely sensitive to small variations in the concentration of the inoculum of the nisin Z plus lacticin 481 producer, with there being a narrow optimum for the release of intracellular aminopeptidases. Plantaricin and lacticin 481 producers seemed the most promising strains to be combined with L. helveticus LH 92 as lactic cultures for cheese manufacture, because of the accelerated release of intracellular aminopeptidases. Copyright ©, International Association for Food Protection

Influence of a bacteriocin-producing lactic culture on the volatile compounds, odour and aroma of Hispánico cheese

The effect of milk inoculation with a bacteriocin-producing lactic culture on Hispánico cheese volatile compounds, odour and aroma was investigated in duplicate experiments, each consisting of two 50-L vats. Milk for experimental cheese was inoculated with 0.5% Lactococcus lactis subsp. lactis INIA 415, a bacteriocin-producing (Bac+) strain harbouring the structural genes of nisin Z and lacticin 481, 0.5% L. lactis subsp. lactis INIA 415-2, a Bac- mutant, and 2% TA052, a commercial Streptococcus thermophilus culture. Lactic cultures for control cheese were 1% L. lactis subsp. lactis INIA 415-2 and 2% TA052. Milk inoculation with bacteriocin-producing culture enhanced the formation of hexanal, 2-methyl-1-propanol, 3-methyl-1-butanol, acetone, 2-pentanone, 2-hexanone and 2-heptanone, but decreased the formation of acetaldehyde, ethanol, 3-methyl-3-buten-1-ol, 3-methyl-2-buten-1-ol, ethyl acetate, ethyl butanoate, ethyl hexanoate, 2-butanone, 2,3-butanedione, 2,3-pentanedione and 3-hydroxy-2-butanone. Experimental cheese received higher scores than control cheese for the odour descriptor "clean cheese" and for the aroma descriptor "sheepy", but quality and intensity of odour and aroma were not significantly influenced by milk inoculation with the bacteriocin-producing culture. © 2004 Elsevier Ltd. All rights reserved