Plate Waste Trends of 5​ th​ -8​ th​ Grade Students at a Residential Environmental Learning Center

This descriptive research determined, using aggregated nonselective plate waste measurements, the characteristics of plate waste generated by 5th-8th grade students visiting Eagle Bluff Environmental Learning Center in Lanesboro, Minnesota over the course of 5 years. The results indicated a positive relationship between plate waste and group size; that groups from rural schools wasted less plate waste than schools from urban or suburban locations; and that groups from private schools wasted less than groups from public school groups. Completely eliminating plate waste is unrealistic, but reducing plate waste lowers user costs, makes program operations more efficient, and enhances a program’s success in meeting nutritional needs of children. (122 words

Targeting the hypoxic fraction of tumours using hypoxia activated prodrugs

The presence of a microenvironment within most tumours containing regions of low oxygen tension or hypoxia has profound biological and therapeutic implications. Tumour hypoxia is known to promote the development of an aggressive phenotype, resistance to both chemotherapy and radiotherapy and is strongly associated with poor clinical outcome. Paradoxically, it is recognised as a high priority target and one therapeutic strategies designed to eradicate hypoxic cells in tumours are a group of compounds known collectively as hypoxia activated prodrugs (HAPs) or bioreductive drugs. These drugs are inactive prodrugs that require enzymatic activation (typically by 1 or 2 electron oxidoreductases) to generate cytotoxic species with selectivity for hypoxic cells being determined by (i) the ability of oxygen to either reverse or inhibit the activation process and (ii) the presence of elevated expression of oxidoreductases in tumours. The concepts underpinning HAP development were established over 40 years ago and have been refined over the years to produce a new generation of HAPs that are under preclinical and clinical development. The purpose of this article is to describe current progress in the development of HAPs focusing on the mechanisms of action, preclinical properties and clinical progress of leading examples

Cellular pharmacology studies of anticancer agents: recommendations from the EORTC-PAMM group

An increasing number of manuscripts focus on the in vitro evaluation of established and novel anti-tumour agents in experimental models. Whilst the design of such in vitro assays is inherently flexible, some of these studies lack the minimum information necessary to critically evaluate their relevance or have been carried out under unsuitable conditions. The use of appropriate and robust methods and experimental design has important implications for generating results that are reliable, relevant, and reproducible. The Pharmacology and Molecular Mechanisms (PAMM) group of the European Organization for Research and Treatment of Cancer (EORTC) is the largest group of academic scientists working on drug development and bundle decades of expertise in this field. This position paper addresses all researchers with an interest in the preclinical and cellular pharmacology of anti-tumour agents and aims at generating basic recommendations for the correct use of compounds to be tested for anti-tumour activity using a range of preclinical cellular models of cancer

Design of optimized hypoxia-activated prodrugs using pharmacokinetic/pharmacodynamic modeling

Hypoxia contributes to resistance of tumors to some cytotoxic drugs and to radiotherapy, but can in principle be exploited with hypoxia-activated prodrugs (HAP). HAP in clinical development fall into two broad groups. Class I HAP (like the benzotriazine N-oxides tirapazamine and SN30000), are activated under relatively mild hypoxia. In contrast, Class II HAP (such as the nitro compounds PR-104A or TH-302) are maximally activated only under extreme hypoxia, but their active metabolites (effectors) diffuse to cells at intermediate O2 and thus also eliminate moderately hypoxic cells. Here, we use a spatially resolved pharmacokinetic/pharmacodynamic (SR-PK/PD) model to compare these two strategies and to identify the features required in an optimal Class II HAP. The model uses a Green’s function approach to calculate spatial and longitudinal gradients of O2, prodrug and effector concentrations, and resulting killing in a digitized 3D tumor microregion to estimate activity as monotherapy and in combination with radiotherapy. An analogous model for a normal tissue with mild hypoxia and short intervesssel distances (based on a cremaster muscle microvessel network) was used to estimate tumor selectivity of cell killing. This showed that Class II HAP offer advantages over Class I including higher tumor selectivity and greater freedom to vary prodrug diffusibility and rate of metabolic activation. The model suggests that the largest gains in class II HAP antitumor activity could be realized by optimizing effector stability and prodrug activation rates. We also use the model to show that diffusion of effector into blood vessels is unlikely to materially increase systemic exposure for realistic tumor burdens and effector clearances. However, we show that the tumor selectivity achievable by hypoxia-dependent prodrug activation alone is limited if dose-limiting normal tissues are even mildly hypoxi

Design and commissioning of the first two CYRCé extension beamlines

International audienceCYRCé is a TR24 cyclotron installed at the Institut Pluridisciplinaire Hubert Curien (IPHC) of Strasbourg operating at energies of 16–25 MeV and at intensities up to 400 μA. The accelerator is used to produce and provide radio-elements for PET and for SPECT. In 2015, IPHC started to develop a platform with the aim of performing radiobiological experiments. The PRECy platform foresees to contain three-to-five experimental stations linked to beamlines expanded from the second exit port of the cyclotron. This extension allows devoting one of the beamlines for detector studies within the framework of the CMS project. The design, the development and the commissioning of the first two beamlines are discussed in this paper