RESUMEN
Personalized risk stratification and treatment may help improve outcomes among patients with diffuse large B-cell lymphoma (DLBCL). We developed a next-generation sequencing (NGS)-based method to assess a range of potential prognostic indicators, and evaluated it using pretreatment plasma samples from 310 patients with previously untreated DLBCL from the GOYA trial (NCT01287741). Variant calls and DLBCL subtyping with the plasma-based method were concordant with corresponding tissue-based methods. Patients with a tumor burden greater than the median (p = .003) and non-germinal center B-cell-like (non-GCB) DLBCL (p = .049) had worse progression-free survival than patients with a tumor burden less than the median or GCB DLBCL. Multi-factor assessment combining orthogonal features from a single pretreatment plasma sample has promise as a prognostic indicator in this setting (p = .085). This minimally invasive plasma-based NGS assay could enable comprehensive prognostic assessment of patients in a clinical setting, with greater accessibility than current methods.
Asunto(s)
Biomarcadores de Tumor , ADN Tumoral Circulante , Secuenciación de Nucleótidos de Alto Rendimiento , Linfoma de Células B Grandes Difuso , Humanos , Linfoma de Células B Grandes Difuso/genética , Linfoma de Células B Grandes Difuso/sangre , Linfoma de Células B Grandes Difuso/mortalidad , Linfoma de Células B Grandes Difuso/diagnóstico , ADN Tumoral Circulante/sangre , ADN Tumoral Circulante/genética , Biomarcadores de Tumor/sangre , Pronóstico , Masculino , Femenino , Persona de Mediana Edad , Anciano , Carga Tumoral , Adulto , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Mutación , Anciano de 80 o más AñosRESUMEN
We used a combination of batch studies and spectroscopic analyses to assess the impacts of aqueous Mn(II) on the solubility and speciation of Zn(II) in anoxic suspensions of hexagonal birnessite at pH 6.5 and 7.5. Introduction of aqueous Mn(II) into pre-equilibrated Zn(II)-birnessite suspensions leads to desorption of Zn(II) at pH 6.5, but enhances Zn(II) sorption at pH 7.5. XAS results show that Zn(II) adsorbs as tetrahedral and octahedral triple-corner-sharing complexes at layer vacancy sites when reacted with birnessite in the absence of Mn(II). Addition of aqueous Mn(II) causes no discernible change in Zn(II) surface speciation at pH 6.5, but triggers conversion of adsorbed Zn(II) into spinel Zn(II)1-xMn(II)xMn(III)2O4 precipitates at pH 7.5. This conversion is driven by electron transfer from adsorbed Mn(II) to structural Mn(IV) generating Mn(III) surface species that coprecipitate with Zn(II) and Mn(II). Our results demonstrate substantial production of these reactive Mn(III) surface species within 30 min of contact of the birnessite substrate with aqueous Mn(II). Their importance as a control on the sorption and redox reactivity of Mn-oxides toward Zn(II) and other trace metal(loid)s in environments undergoing biogeochemical manganese redox cycling requires further study.
Asunto(s)
Manganeso/química , Óxidos/química , Zinc/química , Adsorción , Óxido de Aluminio , Concentración de Iones de Hidrógeno , Óxido de Magnesio , Oxidación-Reducción , Solubilidad , AguaRESUMEN
We investigated the effect of pH (5.5-8.5) on the mineralogical transformation of hexagonal birnessite induced by reaction with aqueous Mn(II) (50-2200 µM), using batch sorption experiments, X-ray diffraction analyses, X-ray absorption and infrared spectroscopic measurements. Samples reacted at pH < 7.0 exhibited disrupted stacking of birnessite sheets, but no mineralogical transformation products were observed. At pH 7.0 and 7.5, reaction with Mn(II) under anoxic conditions caused reductive transformation of birnessite into manganite (γ-MnOOH), whereas at pH 8.0 and 8.5, conversion into hausmannite (Mn3O4) occurred. Feitknechtite (ß-MnOOH) is a major transformation product at low Mn(II) inputs at pH 7.0-8.5, and represents a metastable reaction intermediate that is converted into manganite and possibly hausmannite during further reaction with Mn(II). Thermodynamic calculations suggest that conversion into hausmannite at alkaline pH reflects a kinetic effect where rapid hausmannite precipitation prevents formation of thermodynamically more favorable manganite. In oxic systems, feitknechtite formation due to surface catalyzed oxidation of Mn(II) by O2 increases Mn(II) removal relative to anoxic systems at pH ≥ 7. The results of this study suggest that aqueous Mn(II) is an important control on the mineralogy and reactivity of natural Mn-oxides, particularly in aqueous geochemical environments with neutral to alkaline pH values.