Bortezomib Pharmacogenetic Biomarkers for the Treatment of Multiple Myeloma: Review and Future Perspectives.

Multiple myeloma (MM) is a hematological neoplasm for which different chemotherapy treatments are used with several drugs in combination. One of the most frequently used drugs for the treatment of MM is the proteasome inhibitor bortezomib. Patients treated with bortezomib are at increased risk for thrombocytopenia, neutropenia, gastrointestinal toxicities, peripheral neuropathy, infection, and fatigue. This drug is almost entirely metabolized by cytochrome CYP450 isoenzymes and transported by the efflux pump P-glycoprotein. Genes encoding both enzymes and transporters involved in the bortezomib pharmacokinetic pathway are highly polymorphic. The response to bortezomib and the incidence of adverse drug reactions (ADRs) vary among patients, which could be due to interindividual variations in these possible pharmacogenetic biomarkers. In this review, we compiled all pharmacogenetic information relevant to the treatment of MM with bortezomib. In addition, we discuss possible future perspectives and the analysis of potential pharmacogenetic markers that could influence the incidence of ADR and the toxicity of bortezomib. It would be a milestone in the field of targeted therapy for MM to relate potential biomarkers to the various effects of bortezomib on patients.

The effect of strobilurins on leaf gas exchange, water use efficiency and ABA content in grapevine under field conditions.

Strobilurins are one of the most important classes of agricultural fungicides. In addition to their anti-fungal effect, strobilurins have been reported to produce simultaneous effects in plant physiology. This study investigated whether the use of strobilurin fungicide improved water use efficiency in leaves of grapevines grown under field conditions in a Mediterranean climate in southern Spain. Fungicide was applied three times in the vineyard and measurements of leaf gas exchange, plant water status, abscisic acid concentration in sap ([ABA]), and carbon isotope composition in leaves were performed before and after applications. No clear effect on stomatal conductance, leaf water potential and intrinsic water use efficiency was found after three fungicide applications. ABA concentration was observed to increase after fungicide application on the first day, vanishing three days later. Despite this transient effect, evolution of [ABA] matched well with the evolution of leaf carbon isotope ratio, which can be used as a surrogate for plant water use efficiency. Morning stomatal conductance was negatively correlated to [ABA]. Yield was enhanced in strobilurin treated plants, whereas fruit quality remained unaltered.

Cambios en la citología vaginal posteriores al tratamiento con estrógenos conjugados conforme al peso corporal y distribución del tejido adiposo enb la posmenopausia / Vaginal cytology changes after treatment with conjugated estrogens relating to body weight and adipose tissue distribution in post-menopause

Se estudiaron 30 mujeres histerectomizadas con síntomas climatéricos para analizar la modificación que sufre la citología vaginal en relación con el peso corporal y distribución del tejido adiposo posterior a la administración de estrógenos conjugados como terapia hormonal de reemplazo. Una vez divididas con base en el peso, se encontró que hubo incremento en el valor estrogénico (VE) tanto en aquellas con peso normal como en aquellas con obesidad. Cuando se dividieron con base en la distribución del tejido adiposo sólo hubo incremento en el número de células intermedias y en el VE en el grupo con distribución de la grasa corporal en el segmento inferior. Estos hallazgos indican que más que el peso corporal, la distribución del tejido adiposo es la que influye sobre los cambios en el VE en mujeres que reciben terapia de reemplazo estrogénico