Defining new biotypes in Prostate Cancer for diagnosis, prognosis and therapeutic intervention

El cáncer de próstata (CaP) es el segundo tumor más frecuente en hombres y la sexta causa de muerte por cáncer. Así pues, esta enfermedad constituye un problema socio-sanitario prioritario para el sistema de Salud Pública. Actualmente, las herramientas para orientar el diagnóstico en CaP (PSA y DRE) no son cáncer específicas y presentan distintas limitaciones tales como el alto número de falsos positivos (aproximadamente un 70% en un rango de PSA de 4-10 ng/ml) que dan lugar a complicaciones asociadas con el proceso de biopsia. Además, un gran número de los CaP diagnosticados son tumores de bajo grado implicando un sobre-diagnóstico y sobre-tratamiento de esta enfermedad. Sin embargo, otros CaP tendrán un comportamiento pronóstico más agresivo que dará lugar a la progresión de la enfermedad y en último término a la muerte del paciente. Estas diferencias en el comportamiento clínico del CaP se explican por una alta heterogeneidad molecular presente en este tumor. En este contexto de heterogeneidad molecular nuestro objetivo se centra en la búsqueda de nuevos biomarcadores identificables mediante procedimientos no invasivos y capaces de clasificar a los pacientes con CaP de acuerdo a biotipos moleculares asociados con diferentes parámetros clínico-patológicos y distinto riesgo de progresión. En este trabajo exploramos el papel que tienen los miRNAs como nueva fuente de biomarcadores en CaP y encontramos que el miR-182 y el miR-187 juegan un papel clave en la patogénesis y el desarrollo del CaP en ambos contextos, el diagnóstico (miR-187) y el pronóstico (miR-182). Además, identificamos ALDH1A3, un gen regulado por andrógenos, como diana del miR-187 y como potencial biomarcador en CaP. En nuestra búsqueda de nuevos biomarcadores estudiamos también el papel que tiene el gen SPOP en CaP confirmando su pérdida de expresión y mutaciones en CaP y siendo el primer grupo en describir la asociación de estas alteraciones moleculares con el pronóstico en CaP. Además en nuestro trabajo también intentamos ofrecer nuevas alternativas terapéuticas para el tratamiento del CaP avanzado de acuerdo con el biotipo molecular. Así, nuestro hallazgo de la asociación directa entre IGF-IR y TMPRSS2-ERG y la mayor sensibilidad de este grupo a los inhibidores de IGF-IR nos llevaron a proponer este subgrupo de pacientes como población diana -biotipo- para la inhibición de IGF-IR.Prostate cancer (PCa) is the second most frequent tumor in men and the sixth cause of cancer death. Hence, this disease constitutes a primary socio-sanitary and Public Health problem. Currently, the tools to orientate the PCa diagnosis (PSA and DRE) are not cancer specific and present several limitations such as the high rate of false positives (approximately 70% in the PSA range 4-10 ng/ml) leading to biopsy-associated complications. Furthermore, a high percentage of diagnosed PCa are low-grade tumors meaning a high overdiagnosis and overtreatment. On the other hand, other PCa will have a more aggressive prognostic behavior that could lead to disease progression and patient death. This different clinical behavior is translated into a high molecular heterogeneity. In this context of molecular heterogeneity we aimed to find new biomarkers identifiable by non-invasive procedures able to classify PCa patients according to molecular biotypes associated with different clinico-pathological parameters and risk of progression. In this work we explored the role of miRNAs as a source of new biomarkers in PCa and we found that miR-182 and miR-187 play a key role in the pathogenesis and development of PCa in both the diagnostic (miR-187) and prognostic settings (miR-182). Furthermore, we identified ALDH1A3, an androgen-regulated gene, as a target of miR-187 that also plays a role as biomarker for PCa. In our search for new biomarkers we also assessed the role of SPOP gene in PCa confirming its loss of expression and mutations in PCa but also being the first group to describe the association of these molecular alterations with PCa prognosis. Moreover in our work we also tried to offer new therapeutic alternatives for advanced PCa treatment according to the molecular biotype. Our finding of a direct association between IGF-IR and TMPRSS2-ERG and the higher sensitivity of this group to IGF-IR inhibitor agents lead us to propose this subgroup of patients as a target candidate population -biotype- for IGF-IR inhibition

Trabajo en equipo y relaciones interpersonales en los docentes de la I.E. N° 80820 "Víctor Larco" en Trujillo, 2020

El presente trabajo de investigación tuvo el propósito de establecer la relación existente entre el trabajo en equipo y las relaciones interpersonales en los docentes de la I.E. N°80820 “Víctor Larco”, Trujillo, 2020. Buscando el logro de este propósito se trabajó con una población muestral conformada por 42 docentes, los cuales participaron responsablemente en el estudio. Para comprobar la hipótesis se utilizó un diseño correlacional, el instrumento de recojo de datos que se usó lo constituye el cuestionario de medición sobre el trabajo en equipo y el cuestionario de evaluación de las Relaciones Interpersonal, para encontrar el nivel de correlación se trabajó con el coeficiente de Pearson. Los hallazgos del estudio, nos permitieron conocer que el resultado del cálculo del coeficiente de correlación del trabajo en equipo y las relaciones interpersonales fue de 0.414 ; ubicándose en el nivel de correlación moderado, así mismo el resultado del nivel de significancia fue de 0.006; menor que la p (0.05); concluyéndose que el grado de correlación entre el trabajo en equipo y las relaciones interpersonales en los docentes de la I.E. N° 80820 “Víctor Larco”, de la ciudad de Trujillo, 2020, es positiva moderada y significativa, de acuerdo al valor del coeficiente de Pearson, donde se ha obtenido un valor de r =0.414

Synergistic effect of two formulations of hypochlorous acid in the treatment of 346 chronic ulcers

Our objective was to assess the efficacy of two successive applications of hypochlorous acid, first as a liquid and then as a gel because liquid hypochlorous acid is effective but has little residual effect, while the gel form has more residual power, and compare it with that of other products. An experimental non-randomised study was carried out, treating 346 chronic ulcers in 220 patients. The antiseptic treatment has been divided into ‘hypochlorous acid’ (Clortech), ‘hypochlorous acid liquid + gel’ (Clortech + Microdacyn60R-hydrogel) and ‘Others’ (Prontosan or Chlorhexidine or Microdacyn60R-hydrogel). Bivariate and multivariate studies analysed the characteristics of the patients and their ulcers, including size, symptoms, signs, treatments received and their duration, and so on. The ulcers were complicated, of long evolution, and most had a vascular origin. On average, antiseptic treatment lasted 14 weeks. At the time of their discharge, or last treatment in the clinics, 59% of the ulcers had healed completely, 9.5% worsened, and 6.9% had become infected during this period. In the bivariate and multivariate studies, we took as reference the ‘others’ treatments that showed no significant differences in healing time or infection rates compared with liquid hypochlorous acid 100–500 mg/L alone. However, hypochlorous acid liquid + gel showed a synergistic effect, with a higher probability of achieving complete healing (four times) and a lower probability of infection (a fifth), compared to the ‘other’ antiseptics. In conclusion, a synergistic effect was found with the successive application of hypochlorous acid in liquid followed by gel, an effect that increased healing probability and decreased the risk of the ulcer becoming infecte

Crónica sobre la solución de controversias en materia de inversiones extranjeras (enero-diciembre 2011)

El artículo pone de relieve los últimos desarrollos en materia de arbitraje sobre inversiones extranjeras

The successful use of a submersible ultrasound to confirm pregnancy on free swimming bull sharks, Carcharhinus leucas, in a provisioned shark site

A prototype, fully submersible, high definition ultrasound was used to determine the reproductive state of wild, free-swimming bull sharks, Carcharhinus leucas, at a provisioned shark diving site in Playa del Carmen, Mexico. During two opportunistic dives, the presence of embryos was confirmed in three female sharks (greater than 2.0 m total length) and emphasizes the importance of developing and linking emerging technologies with shark diving sites for the conservation of elasmobranch species

Hypochlorous acid in a double formulation (liquid plus gel) is a key prognostic factor for healing and absence of infection in chronic ulcers. A nonrandomized concurrent treatment study

Background and aims: Diverse protocols prevent infection and/or improve ulcer epithelialization. The existing protocols tend to antagonize the risk factors that promote the chronicity of this type of wound. Hypochlorous acid (HOCl) is used to treat ulcers and wounds because of its antiseptic and noncytotoxic properties. Its liquid form is effective but has little residual effect, while in gel it has more residual power. Methods: An experimental nonrandomized study has been carried out treating 346 chronic ulcers of various etiologies in 220 patients. Ulcer outcomes were originally classified as: "complete healing," "incomplete healing without infection," and "incomplete healing with infection." Various antiseptic solutions were used as ulcers cleaning solutions: liquid HOCl, gel HOCl, polymeric biguanide, or chlorhexidine. Only one was applied to the lesion as monotherapy. But, in other cases, we used a combined HOCl (liquid then gel: bitherapy). Bivariate (Chi-square and variance tests) and multivariate studies (logistic regression) evaluated associations of ulcer characteristics and mono or bitherapy outcomes. Results: Four factors reduce the probability of complete ulcer healing: patient age (odds ratio [OR]: 0.97); weeks of ulcer evolution (OR: 0.99); poor granulation on admission (OR: 0.35); and need for antibiotic therapy (OR: 0.41). One factor favored healing: combined HOCl therapy with liquid plus gel (OR: 4.8). Infections were associated with longer times of evolution (OR: 1.002) and bad odor of the ulcer on admission (OR: 14), but bitreatment with HOCl reduced the risk of infection (OR: 0.3). Conclusion: A double HOCl formulation (liquid plus gel) reduces the probability of poor healing and infection, in chronic ulcers of various etiologies.S

uPA/uPAR and SERPINE1 in head and neck cancer: role in tumor resistance, metastasis, prognosis and therapy

There is strong evidence supporting the role of the plasminogen activator system in head and neck squamous cell carcinoma (HNSCC), particularly of its uPA (urokinase plasminogen activator) / uPAR (urokinase plasminogen activator receptor) and SERPINE1 components. Overexpression of uPA/uPAR and SERPINE1 enhances tumor cell migration and invasion and plays a key role in metastasis development, conferring poor prognosis. The apparent paradox of uPA/uPAR and its inhibitor SERPINE1 producing similar effects is solved by the identification of SERPINE1 activated signaling pathways independent of uPA inhibition. Both uPA/uPAR and SERPINE1 are directly linked to the induction of epithelial-to-mesenchymal transition, the acquisition of stem cell properties and resistance to antitumor agents. The aim of this review is to provide insight on the deregulation of these proteins in all these processes. We also summarize their potential value as prognostic biomarkers or potential drug targets in HNSCC patients. Concomitant overexpression of uPA/uPAR and SERPINE1 is associated with a higher risk of metastasis and could be used to identify patients that would benefit from an adjuvant treatment. In the future, the specific inhibitors of uPA/uPAR and SERPINE1, which are still under development, could be used to design new therapeutic strategies in HNSCCs

A new Diplolepis Geoffroy (Hymenoptera, Cynipidae, Diplolepidini) Species from China: a rare example of a rose gall-inducer of economic significance

A new species of the genus Diplolepis Geoffroy, Diplolepis abei Pujade-Villar & Wang sp. nov. is described on host plant Rosa sertata Rolfe × R. rugosa Thunb. from China with an integrative approach based on molecular and morphological data. Diagnosis, distribution and biology of the new species are included and illustrated. This species is the first known rose gall-inducer of economic importance. A review of Eastern Palearctic species of Diplolepis is given and a key to the Chinese fauna is presented

Differential effects of Anti-TNFα and Anti-α4β7 drugs on circulating dendritic cells migratory capacity in inflammatory bowel disease

Inflammatory bowel disease (IBD) is an idiopathic and chronic disorder that includes ulcerative colitis (UC) and Crohn’s disease (CD). Both diseases show an uncontrolled intestinal immune response that generates tissue inflammation. Dendritic cells (DCs) are antigen-presenting cells that play a key role in tolerance maintenance in the gastrointestinal mucosa. Although it has been reported that DC recruitment by the intestinal mucosa is more prominent in IBD patients, the specific mechanisms governing this migration are currently unknown. In this study, the expression of several homing markers and the migratory profile of circulating DC subsets towards intestinal chemo-attractants were evaluated and the effect of biological drugs with different mechanisms of action, such as anti-TNFα or anti-integrin α4β7 (vedolizumab), on this mechanism in healthy controls (HCs) and IBD patients was also assessed. Our results revealed that type 2 conventional DCs (cDC2) express differential homing marker profiles in UC and CD patients compared to HCs. Indeed, integrin β7 was differentially modulated by vedolizumab in CD and UC. Additionally, although CCL2 displayed a chemo-attractant effect over cDC2, while biological therapies did not modulate the expression of the homing markers, we paradoxically found that anti-TNF-treated cDC2 increased their migratory capacity towards CCL2 in HCs and IBD. Our results therefore suggest a key role for cDC2 migration towards the intestinal mucosa in IBD, something that could be explored in order to develop novel diagnostic biomarkers or to unravel new immunomodulatory targets in IBD.This study has been funded through the Instituto de Salud Carlos III (Sara Borrell fellowships, CD17/00014; CD21/00014), Asociación Española de Gastroenterología (Beca del Grupo Joven), Programa Estratégico Instituto de Biología y Genética Molecular (IBGM Junta de Castilla y León. Ref. CCVC8485), Plan Nacional (PID2019-104218RB-I00) from the Spanish Government, Janssen and MSD