Activity of immunoproteasome inhibitor ONX-0914 in acute lymphoblastic leukemia expressing MLL-AF4 fusion protein.

Proteasome inhibitors bortezomib and carfilzomib are approved for the treatment of multiple myeloma and mantle cell lymphoma and have demonstrated clinical efficacy for the treatment of acute lymphoblastic leukemia (ALL). The t(4;11)(q21;q23) chromosomal translocation that leads to the expression of MLL-AF4 fusion protein and confers a poor prognosis, is the major cause of infant ALL. This translocation sensitizes tumor cells to proteasome inhibitors, but toxicities of bortezomib and carfilzomib may limit their use in pediatric patients.

X-ray microfluorescence for biodistribution studies of nanomedicines.

Currently, the in vivo distribution of drugs is investigated by non-spatial quantitative techniques. With the emergence of personal therapies using nanomedicines, deeper investigations are required to precisely know the in vivo fate of entrapped drugs, especially to predict possible toxicity. Here, we assess the capabilities of SR-μXRF for i) detecting drugs into nanomedicines without adding any marker, ii) mapping their distribution into tissues and iii) locally quantifying the drugs loaded into nanomedicines.

Positively charged cyclodextrins as effective molecular transporters of active phosphorylated forms of gemcitabine into cancer cells.

Positively charged cyclodextrins (PCCDs) are molecular carriers of particular interest for their ability to readily enter into cancer cells. Of main interest, guanidino- and aminoalkyl- PCCDs can be conveniently synthesized and form stable and strong inclusion complexes with various active molecules bearing phosphate groups. We have addressed here the challenge to deliver into cancer cells phosphorylated gemcitabine drugs well known for their instability and inability to permeate cell membranes.

The transfer of (137)Cs, Pu isotopes and (90)Sr to bird, bat and ground-dwelling small mammal species within the Chernobyl exclusion zone.

Protected species are the focus of many radiological environmental assessments. However, the lack of radioecological data for many protected species presents a significant international challenge. Furthermore, there are legislative restrictions on destructive sampling of protected species to obtain such data.

Self-assembly of polyisoprenoyl gemcitabine conjugates: influence of supramolecular organization on their biological activity.

An amphiphilic prodrug of gemcitabine, a cytidine analogue used clinically against various tumors, had been previously synthesized by covalent coupling to squalene, a natural isoprenoid chain. The resulting bioconjugate self-assembled spontaneously in water as nanoparticles, displaying an impressive activity both in vitro and in vivo. The aim of the present study was to determine the influence of the length of the isoprene moiety on the structure of the nanoparticles, in an attempt to establish a relationship between the chemical structure of the prodrug, its supramolecular organization, and its pharmacological activity.

Environmental radiation monitoring in the Chernobyl exclusion zone--history and results 25 years after.

This paper describes results of the radiation environmental monitoring performed in the Chernobyl Exclusion Zone (ChEZ) during the period following the 1986 Chernobyl Nuclear Power Plant accident. This article presents a brief overview of five comprehensive reports generated under Contract No. DE-AC09-96SR18500 (Washington Savannah River Company LLC, Subcontract No.

Radiation ecology issues associated with murine rodents and shrews in the Chernobyl exclusion zone.

This article describes major studies performed by the Chernobyl Center's International Radioecology Laboratory (Slavutich, Ukraine) on radioecology of murine rodents and shrews inhabiting the Chernobyl Exclusion Zone. The article addresses the long-term (1986-2005) and seasonal dynamics of radioactive contamination of animals and reviews interspecies differences in radionuclide accumulations and factors affecting the radionuclide accumulations. It is shown that bioavailability of radionuclides in the "soil-to-plant" chain and a trophic specialization of animals play key roles in determining their actual contamination levels.

Frequency distributions of 90Sr and 137Cs concentrations in an ecosystem of the "Red Forest" area in the Chernobyl exclusion zone.

In the most highly contaminated region of the Chernobyl Exclusion Zone, the "Red Forest" site, the accumulation of the major dose-affecting radionuclides (90Sr and 137Cs) within the components of an ecological system encompassing 3,000 m(2) was characterized. The sampled components included soils (top 0-10 cm depth), Molina caerulea (blue moor grass), Camponotus vagus (carpenter ants), and Pelobates fuscus (spade-footed toad). In a comparison among the components of this ecosystem, the 90Sr and 137Cs concentrations measured in 40 separate grids exhibited significant differences, while the frequency distribution of the values was close to a logarithmically-normal leptokurtic distribution with a significant right-side skew.

Method for simultaneous 90Sr and 137Cs in-vivo measurements of small animals and other environmental media developed for the conditions of the Chernobyl exclusion zone.

To perform in vivo simultaneous measurements of the 90Sr and 137Cs content in the bodies of animals living in the Chernobyl Exclusion Zone (ChEZ), an appropriate method and equipment were developed and installed in a mobile gamma beta spectrometry laboratory. This technique was designed for animals of relatively small sizes (up to 50 g). The 90Sr content is measured by a beta spectrometer with a 0.

Assessment of the radionuclide composition of "hot particles" sampled in the Chernobyl nuclear power plant fourth reactor unit.

Fuel-containing materials sampled from within the Chernobyl Nuclear Power Plant (ChNPP) Unit 4 Confinement Shelter were spectroscopically studied for gamma and alpha content. Isotopic ratios for cesium, europium, plutonium, americium, and curium were identified, and the fuel burn-up in these samples was determined. A systematic deviation in the burn-up values based on the cesium isotopes in comparison with other radionuclides was observed.

Vertical migration of radionuclides in the vicinity of the chernobyl confinement shelter.

Studies of vertical migration of Chernobyl-origin radionuclides in the 5-km zone of the Chernobyl Nuclear Power Plant (ChNPP) in the area of the Red Forest experimental site were completed. Measurements were made by gamma spectrometric methods using high purity germanium (HPGe) detectors with beryllium windows. Alpha-emitting isotopes of plutonium were determined by the measurement of the x-rays from their uranium progeny.

Radiation dose assessment for the biota of terrestrial ecosystems in the shoreline zone of the Chernobyl nuclear power plant cooling pond.

Radiation exposure of the biota in the shoreline area of the Chernobyl Nuclear Power Plant Cooling Pond was assessed to evaluate radiological consequences from the decommissioning of the Cooling Pond. This paper addresses studies of radioactive contamination of the terrestrial faunal complex and radionuclide concentration ratios in bodies of small birds, small mammals, amphibians, and reptiles living in the area. The data were used to calculate doses to biota using the ERICA Tool software.

Overview of the cooperation between the Chernobyl Center's International Radioecology Laboratory in Slavutych, Ukraine, and U.S. research centers between 2000 and 2010.

The International Radioecology Laboratory (IRL) located in Slavutych, Ukraine, was created in 1999 under the initiative of the United States Government and the Government of Ukraine in the framework of international cooperation on evaluation and minimization of consequences of the Chernobyl nuclear power plant (ChNPP) accident. Since the time the IRL was founded, it has participated in a large number of projects, including the following: 1) study of radionuclide accumulation, distribution, and migration in components of various ecological systems of the Chernobyl Exclusion Zone (ChEZ); 2) radiation dose assessments; 3) study of the effects of radiation influence on biological systems; 4) expert analysis of isotopic and quantitative composition of radioactive contaminants; 5) development of new methods and technologies intended for radioecological research; 6) evaluation of future developments and pathways for potential remediation of the ChEZ areas; 7) assistance in provision of physical protection systems for ionizing irradiation sources at Ukrainian enterprises; 8) reviews of open Russian language publications on issues associated with consequences of the ChNPP accident, radioactive waste management, radioecological monitoring, and ChNPP decommissioning; 9) conduct of training courses on problems of radioecology, radiation safety, radioecological characterization of test sites and environmental media, and research methods; 10) conduct of on-site scientific conferences and workshops on the ChEZ and radioecology problems; participation in off-site scientific conferences and meetings; and 11) preparation of scientific and popular science publications and interactions with mass media representatives. This article provides a brief overview of the major achievements resulting from this cooperation between the IRL and U.

Strontium-90 and caesium-137 activity concentrations in bats in the Chernobyl exclusion zone.

Bats are a protected species and as such may be an object of protection in radiological assessments of the environment. However, there have previously been only few radioecological studies of species of bats. In this paper, results for >140 measurements of (90)Sr and (137)Cs in 10 species of bats collected within the Chernobyl zone are presented.