Compuestos vapocrómicos y su uso en sensores medio ambientales de vapores de compuestos orgánicos

Referencia OEPM: P9802085.-- Fecha de solicitud: 07/10/1998.-- Titular: Consejo Superior de Investigaciones Científicas (CSIC), Universidad Pública de Navarra (UPNA).Compuestos vapocrómicos de fórmula general (I) donde L = fosfina, fosfito, arilo, halogenuro; X = ClO4-, CF3SO3-, Cl-, Br-, I-, tht = tetrahidrotiofeno y su uso en el sistema receptor de un dispositivo sensor químico de tipo SAW, QMB, u otros dispositivos que hagan uso de las propiedades de adsorción de estos materiales, en dispositivos sensores químicos ópticos basándose en sus propiedades ópticas y en su inclusión en matrices (sol-gel, poliméricas, etc). [Ver figura en archivo de texto adjunto]Peer reviewe

Estudio de los efectos de algunos psicotropos en el test "Open Field"

Por medio del test "opcn-field" se ha analizado el comportamiento de ratas tratadas con diversos psicotropos ncurolépt icos. antidcpresivos, tranquilizntes, barbitú ricos, psicoana l~pt icos) y asociaciones, entre las que figura la de un IMAO (nialamida) y 5-hidroxitriptofano, precusor de la serotonina cerebral. De los resultados obtenidos se deduce que los neurolépticos dieron lugar a una marcada reducción de la motilidad, en tanto que el clordiacepóxido y el fenobarbilal produjeron el efecto con· trario, probablemente como expresión de un efecto ansiolítico notable. La asociación de nialamida y 5-hidroxitriptofano dió lugar a una reducción muy significativa de la deambulación de las ratas tratadas, sugiriéndose una participación de la serotonina en los circuitos moduladores de la actividad de las ratas. Este descenso de movilidad fue hallado, asimtsmo, con la imipramina, r~lacio nándose también, este fenómeno, con una posible intensificación de sistemas serotoninérgicos. En cuanto a la intervención de los psicotropos sobre las estereotipias y las emisiones de bolos fecales, no se han encontrado resultados capaces de informar con eficacia, sobre la utilidad de estos dos parámetros como medida para la "emotividad"

PIK3CA mutations in advanced cancers: characteristics and outcomes.

PIK3CA mutations are frequently diagnosed in diverse cancers and may predict response to PI3K/AKT/mTOR inhibitors. It remains unclear whether they are associated with other characteristics. We analyzed characteristics and outcome of 90 consecutive patients with diverse advanced tumors and PIK3CA mutations and 180 wild-type PIK3CA controls matched by tumor type, gender, and age referred to the Clinical Center for Targeted Therapy. PIK3CA and MAPK mutations (KRAS, NRAS, and BRAF) were analyzed using polymerase chain reaction-based DNA sequencing. The most frequent PIK3CA mutations were E545K (31/90, 34%), E542K (16/90, 18%) in exon 9, and H1047R (20/90, 22%) in exon 20. PIK3CA mutations compared to wild-type PIK3CA were associated with simultaneous KRAS (p=0.047) and MAPK mutations (p=0.03), but only MAPK mutations were confirmed as having an independent association in multivariate analysis. Rates of lung, bone, liver and brain metastases were similar in PIK3CA-mutant and wild-type patients. Patients with PIK3CA mutations treated on trials with PI3K/AKT/mTOR inhibitors had a higher partial/complete response (PR/CR) rate than wild-type PIK3CA patients treated with their best phase I therapy (10/56, 18% vs. 12/152, 8%; p=0.045), but not a prolonged progression-free survival. Patients with H1047R PIK3CA mutations had higher PR/CR rate with PI3K/AKT/mTOR inhibitors compared to wild-type PIK3CA patients treated with their best phase I therapy (6/16, 38% vs. 12/152, 8%; p=0.003). In conclusion, PIK3CA mutations in diverse cancers were not associated with clinical characteristics, but were correlated with MAPK mutations. PIK3CA mutations, especially, H1047R, were associated with attaining a PR/CR to PI3K/AKT/mTOR pathway inhibitors

Phase I dose-escalation study of the mTOR inhibitor sirolimus and the HDAC inhibitor vorinostat in patients with advanced malignancy.

Preclinical models suggest that histone deacetylase (HDAC) and mammalian target of rapamycin (mTOR) inhibitors have synergistic anticancer activity. We designed a phase I study to determine the safety, maximum tolerated dose (MTD), recommended phase II dose (RP2D), and dose-limiting toxicities (DLTs) of combined mTOR inhibitor sirolimus (1 mg-5 mg PO daily) and HDAC inhibitor vorinostat (100 mg-400 mg PO daily) in patients with advanced cancer. Seventy patients were enrolled and 46 (66%) were evaluable for DLT assessment since they completed cycle 1 without dose modification unless they had DLT. DLTs comprised grade 4 thrombocytopenia (n = 6) and grade 3 mucositis (n = 1). Sirolimus 4 mg and vorinostat 300 mg was declared RP2D because MTD with sirolimus 5 mg caused significant thrombocytopenia. The grade 3 and 4 drug-related toxic effects (including DLTs) were thrombocytopenia (31%), neutropenia (8%), anemia (7%), fatigue (3%), mucositis (1%), diarrhea (1%), and hyperglycemia (1%). Of the 70 patients, 35 (50%) required dose interruption or modification and 61 were evaluable for response. Partial responses were observed in refractory Hodgkin lymphoma (-78%) and perivascular epithelioid tumor (-54%), and stable disease in hepatocellular carcinoma and fibromyxoid sarcoma. In conclusion, the combination of sirolimus and vorinostat was feasible, with thrombocytopenia as the main DLT. Preliminary anticancer activity was observed in patients with refractory Hodgkin lymphoma, perivascular epithelioid tumor, and hepatocellular carcinoma

KRASness and PIK3CAness in Patients with Advanced Colorectal Cancer: Outcome after Treatment with Early-Phase Trials with Targeted Pathway Inhibitors

To evaluate clinicopathologic and molecular features of patients with metastatic colorectal cancer (mCRC) and their outcomes in early-phase trials using pathway-targeting agents.We analyzed characteristics of 238 patients with mCRC referred to the phase 1 trials unit at MD Anderson Cancer Center. KRAS, PIK3CA and BRAF status were tested using PCR-based DNA sequencing.Fifty-one percent of patients harbored KRAS mutations; 15% had PIK3CA mutations. In the multivariate regression model for clinical characteristics KRAS mutations were associated with an increased incidence of lung and bone metastases and decreased incidence of adrenal metastases; PIK3CA mutations were marginally correlated with mucinous tumors (p = 0.05). In the univariate analysis, KRAS and PIK3CA mutations were strongly associated. Advanced Duke's stage (p<0.0001) and KRAS mutations (p = 0.01) were the only significant independent predictors of poor survival (Cox proportional hazards model). Patients with PIK3CA mutations had a trend toward shorter progression-free survival when treated with anti-EGFR therapies (p = 0.07). Eighteen of 78 assessable patients (23%) treated with PI3K/Akt/mTOR axis inhibitors achieved stable disease [SD] ≥6 months or complete response/partial response (CR/PR), only one of whom were in the subgroup (N = 15) with PIK3CA mutations, perhaps because 10 of these 15 patients (67%) had coexisting KRAS mutations. No SD ≥6 months/CR/PR was observed in the 10 patients treated with mitogen-activating protein kinase (MAPK) pathway targeting drugs.KRAS and PIK3CA mutations frequently coexist in patients with colorectal cancer, and are associated with clinical characteristics and outcome. Overcoming resistance may require targeting both pathways

Enriched mannose glycosylation contributes to Act d 2 allergenicity.

Allergens are responsible for the Th2 response in patients as part of complex mixtures of proteins, fatty acids and other molecules. Plant allergens have hitherto been included in several protein families that share no common biochemical features. Their physical, biochemical and immunological characteristics have been widely studied, but no definite conclusion has been reached about what makes a protein an allergen. N-glycosylation is characteristic of plant allergen sources but is not present in mammals

Una Experiencia de iniciación al paralelismo en segundo curso del Grado de Ingeniería Informática

En este artículo se analiza una experiencia de introducción del paralelismo de forma temprana en el Grado de Ingeniería Informática. En la experiencia participan cuatro asignaturas de segundo curso, impartidas por tres departamentos distintos y con la colaboración de un centro de computación. En este curso se realiza la primera aproximación de los alumnos al paralelismo, y se pretende realizar un acercamiento coordinado y práctico a diferentes materias.SUMMARY -- This work presents an experience of early introduction to parallelism in the Degree on Computing Engineering. Four courses of the second year participate in the experience and also a computing centre. The courses are tought by three departments. In the second year the students are introduced to parallelism for the first time, and with our experience we intend to approach different topics of parallelism in a coordinated and practical way.Peer Reviewe

Controlling self-assembling and tumor cell-targeting of protein-only nanoparticles through modular protein engineering

Altres ajuts: EU COST Action CA 17140. Villaverde A received an ICREA ACADEMIA award. Unzueta was supported by PERIS program from the Health Department of la Generalitat de Catalunya.Modular protein engineering is suited to recruit complex and multiple functionalities in single-chain polypeptides. Although still unexplored in a systematic way, it is anticipated that the positioning of functional domains would impact and refine these activities, including the ability to organize as supramolecular entities and to generate multifunctional protein materials. To explore this concept, we have repositioned functional segments in the modular protein T22-GFP-H6 and characterized the resulting alternative fusions. In T22-GFP-H6, the combination of T22 and H6 promotes self-assembling as regular nanoparticles and selective binding and internalization of this material in CXCR4-overexpressing tumor cells, making them appealing as vehicles for selective drug delivery. The results show that the pleiotropic activities are dramatically affected in module-swapped constructs, proving the need of a carboxy terminal positioning of H6 for protein self-assembling, and the accommodation of T22 at the amino terminus as a requisite for CXCR4 cell binding and internalization. Furthermore, the failure of self-assembling as regular oligomers reduces cellular penetrability of the fusions while keeping the specificity of the T22-CXCR4 interaction. All these data instruct how multifunctional nanoscale protein carriers can be designed for smart, protein-driven drug delivery, not only for the treatment of CXCR4 human neoplasias, but also for the development of anti-HIV drugs and other pathologies in which CXCR4 is a relevant homing marker