The Public Repository of Xenografts enables discovery and randomized phase II-like trials in mice

More than 90% of drugs with preclinical activity fail in human trials, largely due to insufficient efficacy. We hypothesized that adequately powered trials of patient-derived xenografts (PDX) in mice could efficiently define therapeutic activity across heterogeneous tumors. To address this hypothesis, we established a large, publicly available repository of well-characterized leukemia and lymphoma PDXs that undergo orthotopic engraftment, called the Public Repository of Xenografts (PRoXe). PRoXe includes all de-identified information relevant to the primary specimens and the PDXs derived from them. Using this repository, we demonstrate that large studies of acute leukemia PDXs that mimic human randomized clinical trials can characterize drug efficacy and generate transcriptional, functional, and proteomic biomarkers in both treatment-naive and relapsed/refractory disease

Działanie antyoksydacyjne i zawartość fenoli w liściach Alnus glutinosa i Alnus incana

Alnus glutinosa and A. incana (Betulaceae), are a small to medium size tree, native to the Northern Hemisphere. The leaves of this species are used in the Republic of Belarus as a source of antioxidants. The aim of this work was investigation of antioxidant activities and total phenolics content in various extracts obtained using water, mixture water with ethanol (from 9:1 to 2:8), and ethanol from A. glutinosa and A. incana leaves. Phenolics content was determined by method with Folin-Ciocalteu reagent and calculated on ellagic acid. The antioxidant activities were measured utilising 1,1-diphenyl-2 picrylhydrazyl (DPPH) radical scavenging test. The highest phenolics concentration was observed in the extracts prepared by extraction with the mixture of water:ethanol from 7:3 to 3:7 and ranged from 17.82% to 18.96% for A. glutinosa and from 10.82% to 12.55% for A. incana. This extracts exhibited the highest free radical scavenging activity ranging from 49.21% to 49.42% and from 41.28% to 41.67% for A. glutinosa and A. incana respectively, comparable to the activity of quercetin. Therefore the mixture of water:ethanol from 7:3 to 3:7 should be used for preparing extracts from this species for medicinal purposes. Results also indicated the existence of a high correlation between antioxidant activity and total phenolics content.Alnus glutinosa i A. incana (Betulaceae), są niewielkimi drzewami, występującymi w stanie naturalnym na obszarach półkuli północnej. Liście obu gatunków są stosowane na terenie Białorusi jako źródło antyoksydantów. Celem naszej pracy było oznaczenie aktywności antyoksydacyjnej oraz zawartości sumy polifenoli w różnych wyciągach otrzymanych z liści Alnus glutinosa i A. incana przez ekstrakcję wodą, mieszaniną wody z etanolem (9:1 do 2:8) i etanolem. Zawartość polifenoli oznaczano metodą z odczynnikiem Folin-Ciocalteu, w przeliczeniu na kwas elagowy. Aktywność antyoksydacyjną mierzono, stosując 1,1–diphenyl–2 picrylhydrazyl radical (DPPH) scavenging test. Zaobserwowano, że najwyższa zawartość polifenoli występowała w wyciągach otrzymanych przez ekstrakcję mieszaninami woda:etanol od 7:3 do 3:7 i wynosiła od 17,82% do 18,96% dla A. glutinosa i od 10,82% do 12,55% dla A. incana. Te ekstrakty wykazywały też najwyższą zdolność zmiatania rodnika w granicach od 49,21% do 49,42% dla A. glutinosa i od 41,28% do 41,67% dla A. incana, porównywalną z aktywnością kwercetyny. Stąd mieszanina woda:etanol od 7:3 do 3:7 powinna być stosowana w celu otrzymywania wyciągów stosowanych w celach leczniczych. Wyniki wskazują też na korelację między aktywnością antyoksydacyjną a zawartością związków fenolowych

The public repository of xenografts enables discovery and randomized phase II-like trials in mice.

More than 90% of drugs with preclinical activity fail in human trials, largely due to insufficient efficacy. We hypothesized that adequately powered trials of patient-derived xenografts (PDX) in mice could efficiently define therapeutic activity across heterogeneous tumors. To address this hypothesis, we established a large, publicly available repository of well-characterized leukemia and lymphoma PDXs that undergo orthotopic engraftment, called the Public Repository of Xenografts (PRoXe). PRoXe includes all de-identified information relevant to the primary specimens and the PDXs derived from them. Using this repository, we demonstrate that large studies of acute leukemia PDXs that mimic human randomized clinical trials can characterize drug efficacy and generate transcriptional, functional, and proteomic biomarkers in both treatment-naive and relapsed/refractory disease