Biomarkers of basal cell carcinoma resistance to methyl-aminolevulinate photodynamic therapy

This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Background Methyl-aminolevulinate photodynamic therapy (MAL-PDT) is an excellent option for the treatment of basal cell carcinoma (BCC). However, up to 25% of cases are resistant to this treatment modality. Objective The aim of this study was to identify potential biomarkers of BCC response to MAL-PDT. Material and methods Clinical, histological, and immunohistochemical (p53, Ki-67, CD-31, COX2, β-catenin, EGFR, and survivin) variables were analyzed in a retrospective study of consecutive BCC patients treated with MAL-PDT at the San Jorge Hospital, Huesca, Spain between January 2006 and December 2015. To deepen on these markers, the effects on p53 and cyclin D1 expression, in vitro response to MAL-PDT of 2 murine BCC cell lines (ASZ and BSZ), was also evaluated. Results The retrospective study examined the response to MAL-PDT of 390 BCCs from 182 patients. The overall clinical response rate was 82.8%, with a mean follow-up time of 35.96 months (SD = 23.46). Immunohistochemistry revealed positive p53 in 84.6% of responders but only 15.4% of nonresponsive tumors (p = 0.011). Tumors with increased peripheral palisading of basal cell islands to immunostaining β-catenin responded poorly to PDT (p = 0.01). In line with our findings in patients, in vitro studies revealed a better response to PDT in the p53-positive ASZ cell line than the p53-negative BSZ cell line (p<0.01). Multivariate analysis revealed that the following variables were significantly associated with response to PDT: age, nBCC, presence of peritumoral inflammatory infiltrate, and p53 immunopositivity. Patients with positive p53 immunostaining were 68.54 times more likely to achieve cure than p53-negative patients (CI95% 2.94–159.8) Conclusion Our finding suggest that certain clinicopathological and immunohistochemical variables, particularly p53 expression, may serve as indicators of BCC response to MAL-PDT, and thus facilitate the selection of patients who are most likely to benefit from this therapyThis project received support from the Instituto de Salud Carlos III and Fondos Feder Europeos, MINECO (FIS PI15/00974). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscrip

Efficient excitation of waveguides in Crank-Nicolson FDTD

In this paper, we present a procedure to calculate the discrete modes propagated with Crank-Nicolson FDTD in metallic waveguides. This procedure enables the correct excitation of this kind of waveguides at any resolution. The problem is reduced to solving an eigenvalue equation, which is performed, both in a closed form, for the usual rectangular waveguide, and numerically in the most general case, validated here with a ridged rectangular waveguide.The work described in this paper and the research leading to these results has received funding from the European Community's Seventh Framework Programme FP7/2007-2013, under grant agreement no 205294 (HIRF SE project), and from the Spanish National Projects TEC2010-20841-C04-04, TEC2007-66698-C04-02, CSD2008- 00068, DEX-530000-2008-105, and the Junta de Andalucia Projects TIC1541 and P09-TIC-5327

An analysis of the Leap-Frog Discontinuous Galerkin method for Maxwell equations

In this paper, we explore the accuracy limits of a Finite-Element Time-Domain method applied to the Maxwell equations, based on a Discontinuous Galerkin scheme in space, and a Leap-Frog temporal integration. The dispersion and dissipation properties of the method are investigated, as well as the anisotropy of the errors. The results of this novel analysis are represented in a practical and comprehensible manner, useful for the application of the method, and for the understanding of the behavior of the errors in Discontinuous Gelerkin Time-Domain methods. A comparison with the Finite-Difference Time-Domain method, in terms of computational cost, is also includedThe work described in this paper and the research leading to these results has received funding from the European Community’s Seventh Framework Programme FP7/2007-2013, under grant agreement no 205294 (HIRF SE project), and from the Spanish National Projects TEC2010-20841-C04-04, CSD2008-00068, and the Junta de Andalucia Project P09-TIC-

Cellular intrinsic factors involved in the resistance of squamous cell carcinoma to photodynamic therapy

Photodynamic therapy (PDT) is widely used to treat non-melanoma skin cancer. However, some patients affected with squamous cell carcinoma (SCC) do not respond adequately to PDT with methyl-δ-aminolevulinic acid (MAL-PDT) and the tumors acquire an infiltrative phenotype and became histologically more aggressive, less differentiated, and more fibroblastic. To search for potential factors implicated in SCC resistance to PDT, we have used the SCC-13 cell line (parental) and resistant SCC-13 cells obtained by repeated MAL-PDT treatments (5th and 10th PDT-resistant generations). Xenografts assays in immunodeficient mice showed that the tumors generated by resistant cells were bigger than those induced by parental cells. Comparative genomic hybridization array (aCGH) showed that the three cell types presented amplicons in 3p12.1 CADM2, 7p11.2 EFGR, and 11q13.3 CCND1 genes. The 5th and 10th PDT-resistant cells showed an amplicon in 5q11.2 MAP3K1, which was not present in parental cells. The changes detected by aCGH on CCND1, EFGR, and MAP3K1 were confirmed in extracts of SCC-13 cells by reverse-transcriptase PCR and by western blot, and by immunohistochemistry in human biopsies from persistent tumors after MAL-PDT. Our data suggest that genomic imbalances related to CCND1, EFGR, and particularly MAP3K1 seem to be involved in the development of the resistance of SCC to PDT. © 2014 The Society for Investigative DermatologyThe work was supported by MINECO (FIS PI12/01253), and Comunidad de Madrid (S2010/BMD-2359). We recognize the valuable contributions of Javier Suela and Juan Cruz Cigudos

Granulomatous hypophysitis by Mycobacterium gordonae in a non HIV-infected patient

Lymphocytic or granulomatous hypophysitis is a rare entity with a difficult diagnosis. Our objective was to report a patient with non-tuberculous granulomatous hypophysitis. An HIV-negative 45-year old man with confusional state, subacute ophthalmoplegia, and clinical and laboratory findings of panhypopituitarism was seen in the emergency unit. A cranial MRI showed a sellar mass suggestive of hypophysitis. After an unsuccessful attempt with steroids and antituberculous drugs the patient died. Post-mortem histopathology revealed granulomatous lesions and restriction fragment length polymorphism analysis confirmed the presence of Mycobacterium gordonae’s DNA. In conclusion, we should consider granulomatous hypophysitis in the differential diagnosis of non-secreting hypophyseal tumors. The etiology of a pituitary granuloma by a non-tuberculous mycobacteria is best reached by histopathological techniques and molecular assays. The optimal therapy is yet to be established

Biodiversity of Gastropod in the Southeastern Gulf of California, Mexico

Currently, studying the environment is important because of the phenomena that take place on the earth every day. That is why it is a priority to carry out studies that relate environmental changes to the biology of organisms. This allows us to know the interactions with the environment, and in this way solve, reduce or prevent ecological and economic problems, if they are organisms with a commercial value. The objective of this investigation is to determine ecological parameters of the gastropod community from the intertidal zone on five islands from the Gulf of California, México, to model the diversity, distribution and abundance of malacological fauna. We considered to evaluate the Shannon-Wiener diversity (H′), Pielou’s of evenness (J) and the Margalef species richness indexes, in order to evaluate through an analysis from biotic and abiotic factors, the species status that was collected from the exposed and non-exposed zone tidal. The generated data were contemplated from a year-based biodiversity project (2016–2017) on the following islands: Patos, Bledos, Bleditos, Tunosa, and Mazocahui which belong to the Ohuira lagoon in Ahome, Sinaloa, southeast of the Gulf of California, México. Likewise a status about the importance of gastropods is mentioned for the study area

Palaeolithic – Epipalaeolithic Seapeople of the Southern Iberian coast (Spain): an overview

The significance of coastal areas to human survival and expansion on the planet is undeniable. Their ecological diversity and their use as communication routes are some of their most distinctive qualities. However, the evidence of exploitation of these resources has had an uneven preservation, which is limited to certain regions and more recent events, mainly sites with deposits from the Upper Pleistocene and Holocene. This paper analyses the data available on the use of marine resources between MIS 6 and MIS 1 (c. 150 – 9 ka BP) in Southern Iberia, one of the first regions in Europe where marine faunal remains were discovered, in archaeological deposits from Middle and Upper Palaeolithic. Therefore their presence here has not been a criterion of separation between Neanderthals and Modern humans, but it may be relevant to analyze changes in the use of small preys or assess the economic diversification in regions where this came at an early date. One of the aims of this study was to evaluate the diachronic trends of the different palaeobiological marine remains recovered from coastal and inland archaeological sites. This preliminary extract indicates that the analysis of marine resource exploitation cannot be classed as a mere listing of palaeobiological remains. This information may be relevant in the initial stages, but it is insufficient in the evaluation of techno-economic and sociocultural transformations that can be linked to the use of marine resources. The distribution of palaeobiological marine remains differs over time and also according to the location of the sites with respect to the changing coastline throughout the period analysed. The known sites that preserve evidence of the use of marine resources as a food source are located mainly on the present coastline, or in a range of less than 10 km. Invertebrate remains have been identified in most, whereas fish, bird and mammal bones only in certain sites. Molluscs used as ornaments or pendants and containers are more widely distributed than other species used for food. Because these data must be contextualized, bone and stone tools linked to the exploitation of the marine environment have been added to the palaeobiological information, drawing inferences based on the analogy between both ethnologically and archaeologically documented tools. Symbolic expressions have also been studied, given the significant number of painted and engraved marine fauna depictions, specifically pisciforms and mammals, found in southern Iberia. Lastly, available molecular data has also been evaluated, from the results of isotope analysis on human remains. This combination of palaeobiological, techno-economic, graphic-symbolic and molecular data, allows a first assessment of the use of marine resources in the region

Tocilizumab in refractory Caucasian Takayasu's arteritis: a multicenter study of 54 patients and literature review

Objective: To assess the efficacy and safety of tocilizumab (TCZ) in Caucasian patients with refractory Takayasu's arteritis (TAK) in clinical practice. Methods: A multicenter study of Caucasian patients with refractory TAK who received TCZ. The outcome variables were remission, glucocorticoid-sparing effect, improvement in imaging techniques, and adverse events. A comparative study between patients who received TCZ as monotherapy (TCZMONO) and combined with conventional disease modifying anti-rheumatic drugs (cDMARDs) (TCZCOMBO) was performed. Results: The study comprised 54 patients (46 women/8 men) with a median [interquartile range (IQR)] age of 42.0 (32.5-50.5) years. TCZ was started after a median (IQR) of 12.0 (3.0-31.5) months since TAK diagnosis. Remission was achieved in 12/54 (22.2%), 19/49 (38.8%), 23/44 (52.3%), and 27/36 (75%) patients at 1, 3, 6, and 12 months, respectively. The prednisone dose was reduced from 30.0 mg/day (12.5-50.0) to 5.0 (0.0-5.6) mg/day at 12 months. An improvement in imaging findings was reported in 28 (73.7%) patients after a median (IQR) of 9.0 (6.0-14.0) months. Twenty-three (42.6%) patients were on TCZMONO and 31 (57.4%) on TCZCOMBO: MTX (n = 28), cyclosporine A (n = 2), azathioprine (n = 1). Patients on TCZCOMBO were younger [38.0 (27.0-46.0) versus 45.0 (38.0-57.0)] years; difference (diff) [95% confidence interval (CI) = -7.0 (-17.9, -0.56] with a trend to longer TAK duration [21.0 (6.0-38.0) versus 6.0 (1.0-23.0)] months; diff 95% CI = 15 (-8.9, 35.5), and higher c-reactive protein [2.4 (0.7-5.6) versus 1.3 (0.3-3.3)] mg/dl; diff 95% CI = 1.1 (-0.26, 2.99). Despite these differences, similar outcomes were observed in both groups (log rank p = 0.862). Relevant adverse events were reported in six (11.1%) patients, but only three developed severe events that required TCZ withdrawal. Conclusion: TCZ in monotherapy, or combined with cDMARDs, is effective and safe in patients with refractory TAK of Caucasian origin.Funding: This work was partially supported by RETICS Programs, RD08/0075 (RIER), RD12/0009/0013 and RD16/0012 from “Instituto de Salud Carlos III” (ISCIII) (Spain)

XLI Jornadas de teatro clásico

Jornadas organizadas por el Instituto Almagro de teatro clásico, dedicadas a la figura de Agustín Moreto

Revista de Vertebrados de la Estación Biológica de Doñana

Catálogo descriptivo de los anfibios y reptiles de CubaEvolución estacional de la comunidad de aves en un robledal de Sierra NevadaComposición de la comunidad de aves en pinares del Parque Nacional de Doñana (suroeste de España).Alimentación de la pagaza piconegra (Gelochelidon nilotica) en las marismas del GuadalquivirContaminación xenobiótica del Parque Nacional de Doñana. III. Residuos de insecticidas organoclorados, bifenilos policlorados y metales pesados en ciconiformesAlimentación de la lechuza común Tyto alba en la cuenca del Duero, EspañaEstudio de una población rural de (Mus musculus L.) I. La probabilidad de captura y la estima numéricLa reproducción en Gazella dorcasIncidencia del Nemátodo parásito Skrjabingylus Leuckart, 1842 sobre el Mustela en España.Desplazamientos de ungulados silvestres a través de una zona de ecotono en Doñana.Etograma de la cabra montés (Capra pyrenaica) y comparación con otras especies.Sobre comportamiento agresivo de Triturus marmoratus en época de celoEmbarrancamiento masivo de ejemplares de tortuga lad (Dermochelys coriacea L.) en las costas de Ceuta (España, norte de África)Sobre un ejemplar melánico de Podarcis hispanica (Steindachner, 1870)Nuevos datos sobre la distribución de cuatro especies de reptiles en la provincia de Cádiz.Algunos datos sobre la nidificación de Ciconia nigra L. en sierra Morena (S. España)Observación del halcón de Eleonor (Falco eleonorae) en el centro de EspañaNueva localidad de cría del pájaro moscón (Remiz pendulinus) en la Península IbéricaRegistro de aves en el sur de BoliviaNidificación del paiño de Madeira Oceanodroma castro (Harcourt, 1851) en las Islas Canarias.Observación primaveral de Phalaropus fulicarius L. en el SO de EspañaNuevos datos sobre la presencia del nóctulo gigante Nyctalus lasiopterus (Chiroptera, vespertilionidae) en EspañaNote sur l'alimentation de Martes martes a Menorca (Baleares).Peer reviewe