Nanotechnology in radiation oncology: The need for implantable nano dosimeters for in-vivo real time measurements

International audienceRapidly advancing technology provides successive generations of irradiation techniques and modalities of cancer treatment in radiation oncology. Most of these techniques are able to deliver higher doses per fraction than the standard 2 Gy per day. The complexity of these new techniques involves hundreds of parameters for the delivery of each beam making quality assurance increasingly demanding. A direct assessment of the "final product", namely the absorbed dose, would be extremely useful if easy to obtain. Thus, a real need exists for dosimeters able to provide direct and real time measurements within the target volume. Nanotechnology is a relatively new field, and in some ways raises new technological aspirations, especially in the field of medical applications for cancer treatment. In this paper we argue the need for an implantable " nano-dosimeter " based on nanotechnology to monitor the delivered dose, combining all the ideal features such a future tool should have for quality assurance in radiation oncology

Biological systems: from water radiolysis to carbon ion radiotherapy

International audienceHadron therapy is an innovative cancer treatment method based on the acceleration of light ions at high energy. In addition to their interesting profile of dose deposition, which ensures accurate targeting of localized tumors, carbon ions offer biological properties that lead to an efficient treatment for radio-and chemo-resistant tumors and to provide a boost for tumors in hypoxia. This paper is a short review of the progress in theoretical, experimental, fundamental and applied research, aiming at understanding the origin of the biological benefits of light ions better. As a limit of such a vast and multidisciplinary domain, this review adopts the point of view of the physicists, leaning on results obtained in connection with CIMAP's IRRABAT platform. 1. Introduction Interaction of fast ions with biological systems constitutes one aspect of the interdisciplinary researches performed with ion-beam facilities. This domain is as rich as it is complex since it encompasses several orders of magnitude in both space and time. The shortest space and time scale corresponds to atomic collisions, which may be as short as 10 −18 s for the interaction of fast ions with individual atoms. At the opposite end of this domain, late effects – like cancer induction, chromosomal instability or organ dysfunctions – may appear or remain several years after irradiations. While irradiations may be limited to a very localized region, the whole behavior of an organ may be affected, possibly leading to human death, in particular when the irradiation dose and spatial extension are high. Between these two extreme scales, stands a great number of mechanisms, including for instance: the transport of the primary ejected electrons, the relaxation of the ionized and excited molecules, which may lead to direct damage in biological targets and to radical species and associated biochemical reactions. These early physical and chemical stages are followed by numerous and complex cell responses, such as the triggering of mechanisms to check DNA, to repair its damage, to manage the oxidative stress or to induce cell death. The numerous biological endpoints that have been studied reveal the complexity and the diversity of this biological response. These endpoints may involve particular structures of cells at the molecular scale (tracking of protein activities, damage in DNA, protein or lipid) or at the sub-cellular scale (chromosomes, nucleus, membranes, mitochondria.. .) and may concern cell organization (3D cell culture, tissues, organs, body). The domain of low dose

A Preliminary Study For A Biomechanical Model Of The Respiratory System

Engineering and Computational Sciences for Medical Imaging in Oncology - ECSMIO is the special session 1 of International Conference on Computer Vision Theory and Applications - VISAPP 2010International audienceTumour motion is an essential source of error for treatment planning in radiation therapy. This motion is mostly due to patient respiration. To account for tumour motion, we propose a solution that is based on the biomechanical modelling of the respiratory system. To compute deformations and displacements, we use continuous mechanics laws solved with the finite element method. In this paper, we propose a preliminary study of a complete model of the respiratory system including lungs, chest wall and a simple model of the diaphragm. This feasibility study is achieved by using the data of a "virtual patient". Results are in accordance with the anatomic reality, showing the feasibility of a complete model of the respiratory system

Receptor guanylyl cyclase (RGC) family (version 2020.3) in the IUPHAR/BPS Guide to Pharmacology Database

The mammalian genome encodes seven guanylyl cyclases, GC-A to GC-G, that are homodimeric transmembrane receptors activated by a diverse range of endogenous ligands. These enzymes convert guanosine-5'-triphosphate to the intracellular second messenger cyclic guanosine-3',5'-monophosphate (cyclic GMP). GC-A, GC-B and GC-C are expressed predominantly in the cardiovascular system, skeletal system and intestinal epithelium, respectively. GC-D and GC-G are found in the olfactory neuropepithelium and Grueneberg ganglion of rodents, respectively. GC-E and GC-F are expressed in retinal photoreceptors

Receptor guanylyl cyclase (RGC) family in GtoPdb v.2023.1

The mammalian genome encodes seven guanylyl cyclases, GC-A to GC-G, that are homodimeric transmembrane receptors activated by a diverse range of endogenous ligands. These enzymes convert guanosine-5'-triphosphate to the intracellular second messenger cyclic guanosine-3',5'-monophosphate (cyclic GMP). GC-A, GC-B and GC-C are expressed predominantly in the cardiovascular system, skeletal system and intestinal epithelium, respectively. GC-D and GC-G are found in the olfactory neuropepithelium and Grueneberg ganglion of rodents, respectively. GC-E and GC-F are expressed in retinal photoreceptors

The Concise Guide to PHARMACOLOGY 2023/24:Catalytic receptors

The Concise Guide to PHARMACOLOGY 2023/24 is the sixth in this series of biennial publications. The Concise Guide provides concise overviews, mostly in tabular format, of the key properties of approximately 1800 drug targets, and nearly 6000 interactions with about 3900 ligands. There is an emphasis on selective pharmacology (where available), plus links to the open access knowledgebase source of drug targets and their ligands (https://www.guidetopharmacology.org/), which provides more detailed views of target and ligand properties. Although the Concise Guide constitutes almost 500 pages, the material presented is substantially reduced compared to information and links presented on the website. It provides a permanent, citable, point-in-time record that will survive database updates. The full contents of this section can be found at http://onlinelibrary.wiley.com/doi/10.1111/bph.16180. Catalytic receptors are one of the six major pharmacological targets into which the Guide is divided, with the others being: G protein-coupled receptors, ion channels, nuclear hormone receptors, enzymes and transporters. These are presented with nomenclature guidance and summary information on the best available pharmacological tools, alongside key references and suggestions for further reading. The landscape format of the Concise Guide is designed to facilitate comparison of related targets from material contemporary to mid-2023, and supersedes data presented in the 2021/22, 2019/20, 2017/18, 2015/16 and 2013/14 Concise Guides and previous Guides to Receptors and Channels. It is produced in close conjunction with the Nomenclature and Standards Committee of the International Union of Basic and Clinical Pharmacology (NC-IUPHAR), therefore, providing official IUPHAR classification and nomenclature for human drug targets, where appropriate.</p

Nitrite circumvents platelet resistance to nitric oxide in patients with heart failure preserved ejection fraction and chronic atrial fibrillation

Aims: Heart failure (HF) is a pro-thrombotic state. Both platelet and vascular responses to nitric oxide (NO) donors are impaired in HF patients with reduced ejection fraction (HFrEF) compared to healthy volunteers (HV) due to scavenging of NO, and possibly also reduced activity of the principal NO sensor, soluble guanylate cyclase (sGC), limiting the therapeutic potential of NO donors as anti-aggregatory agents. Previous studies have shown that nitrite inhibits platelet activation presumptively after its reduction to NO, but the mechanism(s) involved remain poorly characterized. Our aim was to compare the effects of nitrite on platelet function in HV vs. HF patients with preserved ejection fraction (HFpEF) and chronic atrial fibrillation (HFpEF-AF), vs. patients with chronic AF without HF, and to assess whether these effects occur independent of the interaction with other formed elements of blood. Methods and Results: Platelet responses to nitrite and the NO donor sodium nitroprusside (SNP) were compared in age-matched HV controls (n = 12), HFpEF-AF patients (n = 29) and chronic AF patients (n = 8). Anti-aggregatory effects of nitrite in the presence of NO scavengers/sGC inhibitor were determined and vasodilator-stimulated phosphoprotein (VASP) phosphorylation was assessed using Western blotting. In HV and chronic AF, both nitrite and SNP inhibited platelet aggregation in a concentration-dependent manner. Inhibition of platelet aggregation by the NO donor SNP was impaired in HFpEF-AF patients compared to healthy and chronic AF individuals, but there was no impairment of the anti-aggregatory effects of nitrite. Nitrite circumvented platelet NO resistance independently of other blood cells by directly activating sGC and phosphorylating VASP. Conclusion: We here show for the first time that HFpEF-AF (but not chronic AF without HF) is associated with marked impairment of platelet NO responses due to sGC dysfunction and nitrite circumvents the “platelet NO resistance” phenomenon in human HFpEF, at least partly, by acting as a direct sGC activator independent of NO

The Concise guide to pharmacology 2019/20: Enzymes

The Concise Guide to PHARMACOLOGY 2019/20 is the fourth in this series of biennial publications. The Concise Guide provides concise overviews of the key properties of nearly 1800 human drug targets with an emphasis on selective pharmacology (where available), plus links to the open access knowledgebase source of drug targets and their ligands (www.guidetopharmacology.org), which provides more detailed views of target and ligand properties. Although the Concise Guide represents approximately 400 pages, the material presented is substantially reduced compared to information and links presented on the website. It provides a permanent, citable, point-in-time record that will survive database updates. The full contents of this section can be found at http://onlinelibrary.wiley.com/doi/10.1111/bph.14752. Enzymes are one of the six major pharmacological targets into which the Guide is divided, with the others being: G protein-coupled receptors,ion channels, nuclear hormone receptors, catalytic receptors and transporters. These are presented with nomenclature guidance and summary information on the best available pharmacological tools, alongside key references and suggestions for further reading. The landscape format of the Concise Guide is designed to facilitate comparison of related targets from material contemporary to mid-2019, and supersedes data presented in the 2017/18, 2015/16 and 2013/14 Concise Guides and previous Guides to Receptors and Channels. It is produced in close conjunction with the International Union of Basic and Clinical Pharmacology Committee on Receptor Nomenclature and Drug Classification (NC-IUPHAR), therefore, providing official IUPHAR classification and nomenclature for human drug targets, where appropriate.Molecular Physiolog

Formalization and theoretical analysis of the Local Effect Model

International audienceThe Local Effect Model (LEM) is a track-structure model that was developed to predict the biological response of a cell to irradiation with any ion. Because it needs to be studied both experimentally and theoretically, a mathematical formalization of the LEM based on three main postulates and three secondary approximations is proposed for a more detailed analysis. The general relationship that links cell survival to the mean number of lethal events is deduced. A Monte Carlo simulation is also proposed to calculate the local dose. It is shown that the local dose is highly heterogeneous even for uniform X irradiations. This observation raises questions about the estimation of the density of ion-induced lethal events from the expression of cell survival after exposure to X rays. Finally, it is shown that a strict theory of local effects based solely on local dose cannot reproduce nonlinear structures in cell survival curves, such as the shoulders observed after low-LET irradiation

NanOx, a new multiscale model to predict biological dose for hadrontherapy

International audienc