RESUMEN
Personalized peptide vaccination (PPV) is an attractive approach to cancer immunotherapy with strong immune-boosting effects conferring significant clinical benefit. However, as with most therapeutic agents, there is a difference in clinical efficacy among patients receiving PPV. Therefore, a useful biomarker is urgently needed for prognosticating clinical outcomes to preselect patients who would benefit the most from PPV. In this retrospective study, to detect a molecular prognosticator of clinical outcomes for PPV, we analyzed whole-genome gene expression profiles of peripheral blood mononuclear cells (PBMCs) in castration-resistant prostate cancer (CRPC) patients before administration of PPV. Cox regression analysis revealed that mRNA expression of myeloperoxidase, haptoglobin, and neutrophil elastase was significantly associated with overall survival (OS) among vaccinated CRPC patients (adjusted P < 0.01). By promoter sequence analysis of these three genes, we found that rs5472 of haptoglobin (HP), an acute-phase plasma glycoprotein, was strongly correlated to OS of vaccinated CRPC patients (P = 0.0047, hazard ratio 0.47; 95 % confidence interval 0.28-0.80). Furthermore, both HP mRNA expression in PBMCs and protein level in plasma of CRPC patients before administration of PPV exhibited rs5472 dependence (P < 0.001 for mRNA expression and P < 0.05 for protein level). Our findings suggest that rs5472 may play an important role in the immune response to PPV via regulation of HP. Thus, we concluded that rs5472 is a potential prognostic biomarker for PPV.
Asunto(s)
Biomarcadores de Tumor/genética , Vacunas contra el Cáncer/uso terapéutico , Haptoglobinas/genética , Polimorfismo Genético , Neoplasias de la Próstata Resistentes a la Castración/terapia , Vacunas de Subunidad/uso terapéutico , Humanos , Masculino , Regiones Promotoras Genéticas/genética , Neoplasias de la Próstata Resistentes a la Castración/diagnóstico , ARN Mensajero/genética , Estudios Retrospectivos , Resultado del TratamientoRESUMEN
Arsenic water pollution is a big issue worldwide. Determination of inorganic arsenic in each oxidation state is important because As(III) is much more toxic than As(V). An automated arsenic measurement system was developed based on complete vaporization of As by a sequential procedure and collection/preconcentration of the vaporized AsH(3), which was subsequently measured by a flow analysis. The automated sensitive method was applied to monitoring As(III) and As(V) concentrations in contaminated water standing overnight. Behaviors of arsenics were investigated in different conditions, and unique time dependence profiles were obtained. For example, in the standing of anaerobic water samples, the As(III) concentration immediately began decreasing whereas dead time was observed in the removal of As(V). In normal groundwater conditions, most arsenic was removed from the water simply by standing overnight. To obtain more effective removal, the addition of oxidants and use of steel wools were investigated. Simple batch wise treatments of arsenic contaminated water were demonstrated, and detail of the transitional changes in As(III) and As(V) were investigated.
Asunto(s)
Arsénico/aislamiento & purificación , Análisis de Inyección de Flujo/métodos , Contaminantes Químicos del Agua/aislamiento & purificación , Purificación del Agua/métodos , Arseniatos/análisis , Arseniatos/aislamiento & purificación , Arsénico/análisis , Concentración de Iones de Hidrógeno , Contaminantes Químicos del Agua/análisis , Purificación del Agua/instrumentaciónRESUMEN
In this work, a new analytical method for gasifiable compounds based on sequential hydride generation flow injection analysis (SHGFIA) was applied to water analysis and leaching investigation. For water analysis, it was confirmed that 1 µg L(-1) As(III) and As(V) were stable for a few days when EDTA was added in the sample waters. Dissolved As(III) and total arsenic (As(III)+As(V)) were converted to AsH(3) in neutral and acidic medium, respectively, to transfer to a miniature gas scrubber (100 µL in absorber volume). The collected arsenic was successively measured by flow analysis based on molybdenum blue chemistry. With this system, changes in As(III) and As(V) concentrations of water placed with arsenic-contaminated-sediment was monitored in near real time. From these data, kinetic analyses were carried out and kinetic constant was obtained from plot of ln{(C(∞)-C)/C(∞)} where C and C(∞) were leached arsenic concentration and its final concentration, respectively. It was found that rate of As(III) leaching was much faster than that of As(V) while As(V) leached more in amount compared to As(III). In this work, it was demonstrated that kinetic investigation is also one of the important application of flow analysis. The SHGFIA system showed excellent performance for leaching analysis of arsenic with discrimination of As(III) and As(V).
RESUMEN
Students who wanted to quit smoking were invited to partner with teachers/support persons to identify the meaningful patterns of their lives. The theoretical framework guiding the study was Newman's theory of health as expanding consciousness from the perspective of the unitary-transformative paradigm in nursing science. Student participants shared the meaningful relationships and events of their lives with their supportive partners, and together they reflected on the patterns of the students' lives. Two similarities among the individual patterns were found: a difficult experience in interpersonal relationships at some point in their lives and the initiation of smoking in their search for connectedness with friends. In the dialectic process, students experienced insight regarding their evolving patterns and made transformative changes in their lives, reflecting varying levels of tobacco control.
Asunto(s)
Conducta del Adolescente/psicología , Relaciones Interpersonales , Relaciones Enfermero-Paciente , Prevención del Hábito de Fumar , Apoyo Social , Estudiantes/psicología , Adolescente , Actitud Frente a la Salud , Femenino , Humanos , Japón , Masculino , Modelos PsicológicosRESUMEN
Hydride generation to form arsine and in-line preconcentration of the arsine into an alkaline KMnO4 receiver followed by molybdenum blue (MB) colorimetric determination of the arsenate formed is proposed for the highly sensitive and separate measurement of total inorganic As and As(III). Reduction of As to AsH3 is carried out by NaBH4; when the reduction is carried out at pH 1, all the inorganic As is reduced to AsH3, and when carried out at pH 7, only As(III) is reduced. Reductions at the two different pH levels are carried out in two different arsine generators simultaneously using constant addition of NaBH4 with solenoid pumps. The AsH3 is collected by individual porous membrane diffusion scrubbers filled with a stationary solution of KMnO4, and the contents of the two scrubbers sequentially enter a flow analysis stream. MB is formed by merging with a ammonium molybdate-ascorbic acid reagent, passing through a heated reactor, and is then measured by a LED/photodiode-based absorbance detector. Robustness was confirmed for total As using three types of certified natural water samples. Speciation analysis data from well water samples analyzed by this method agree well with HPLC-ICPMS measurements in a different laboratory. The system has been successfully applied to field measurements of As(III) and As(V), where levels were significantly below 1 mug/L. For a 20-mL sample, the limits of detection (LODs) for this inexpensive instrument are 0.3 microg/L for both As(III) and total As. When an 80-mL sample is analyzed, LODs are 0.07 microg/L As(III) and 0.09 microg/L total As. The general approach should be applicable to many other analyte species of interest that can be isolated from the matrix by the formation of a suitable volatile compound that can be recaptured.