Radioactive Beams in Particle Therapy: Past, Present, and Future

Heavy ion therapy can deliver high doses with high precision. However, image guidance is needed to reduce range uncertainty. Radioactive ions are potentially ideal projectiles for radiotherapy because their decay can be used to visualize the beam. Positron-emitting ions that can be visualized with PET imaging were already studied for therapy application during the pilot therapy project at the Lawrence Berkeley Laboratory, and later within the EULIMA EU project, the GSI therapy trial in Germany, MEDICIS at CERN, and at HIMAC in Japan. The results show that radioactive ion beams provide a large improvement in image quality and signal-to-noise ratio compared to stable ions. The main hindrance toward a clinical use of radioactive ions is their challenging production and the low intensities of the beams. New research projects are ongoing in Europe and Japan to assess the advantages of radioactive ion beams for therapy, to develop new detectors, and to build sources of radioactive ions for medical synchrotrons

Genome-wide multi-parametric analysis of H2AX or γH2AX distributions during ionizing radiation-induced DNA damage response

Background: After induction of DNA double strand breaks (DSBs), the DNA damage response (DDR) is activated. One of the earliest events in DDR is the phosphorylation of serine 139 on the histone variant H2AX (gH2AX) catalyzed by phosphatidylinositol 3-kinases-related kinases. Despite being extensively studied, H2AX distribution[1] across the genome and gH2AX spreading around DSBs sites[2] in the context of different chromatin compaction states or transcription are yet to be fully elucidated. Materials and methods: gH2AX was induced in human hepatocellular carcinoma cells (HepG2) by exposure to 10 Gy X-rays (250 kV, 16 mA). Samples were incubated 0.5, 3 or 24 hours post irradiation to investigate early, intermediate and late stages of DDR, respectively. Chromatin immunoprecipitation was performed to select H2AX, H3 and gH2AX-enriched chromatin fractions. Chromatin-associated DNA was then sequenced by Illumina ChIP-Seq platform. HepG2 gene expression and histone modification (H3K36me3, H3K9me3) ChIP-Seq profiles were retrieved from Gene Expression Omnibus (accession numbers GSE30240 and GSE26386, respectively). Results: First, we combined G/C usage, gene content, gene expression or histone modification profiles (H3K36me3, H3K9me3) to define genomic compartments characterized by different chromatin compaction states or transcriptional activity. Next, we investigated H3, H2AX and gH2AX distributions in such defined compartments before and after exposure to ionizing radiation (IR) to study DNA repair kinetics during DDR. Our sequencing results indicate that H2AX distribution followed H3 occupancy and, thus, the nucleosome pattern. The highest H2AX and H3 enrichment was observed in transcriptionally active compartments (euchromatin) while the lowest was found in low G/C and gene-poor compartments (heterochromatin). Under physiological conditions, the body of highly and moderately transcribed genes was devoid of gH2AX, despite presenting high H2AX levels. gH2AX accumulation was observed in 5’ or 3’ flanking regions, instead. The same genes showed a prompt gH2AX accumulation during the early stage of DDR which then decreased over time as DDR proceeded. Finally, during the late stage of DDR the residual gH2AX signal was entirely retained in heterochromatic compartments. At this stage, euchromatic compartments were completely devoid of gH2AX despite presenting high levels of non-phosphorylated H2AX. Conclusions: We show that gH2AX distribution ultimately depends on H2AX occupancy, the latter following H3 occupancy and, thus, nucleosome pattern. Both H2AX and H3 levels were higher in actively transcribed compartments. However, gH2AX levels were remarkably low over the body of actively transcribed genes suggesting that transcription levels antagonize gH2AX spreading. Moreover, repair processes did not take place uniformly across the genome; rather, DNA repair was affected by genomic location and transcriptional activity. We propose that higher H2AX density in euchromaticcompartments results in high relative gH2AXconcentration soon after the activation of DDR, thus favoring the recruitment of the DNA repair machinery to those compartments. When the damage is repaired and gH2AX is removed, its residual fraction is retained in the heterochromatic compartments which are then targeted and repaired at later times

El teletrabajo

Trabajo final de graduación de 92 páginas en formato pdfDesde principios de la pasada década, el desarrollo de las tecnologías de la informática y las telecomunicaciones en los sistemas productivos se ha constituido en uno de los vectores estructurantes del mundo de la información y las relaciones humanas, afectando consecuentemente las relaciones del trabajo. El mundo actual se encuentra sumergido en una época de transición y crisis, parece contemplar el final de lo que conocemos como sociedad industrial y asistir al inicio de un cambio social que variará las formas de vivir y trabajar, generando una nueva era en la evolución humana, un nuevo modelo de sociedad, denominada la sociedad de la información. A medida de que la sociedad y la tecnología avanzan nacen nuevas formas y modalidades de trabajo que irán imponiéndose de acuerdo a la necesidad de cada ciudadano de estructurar su vida a mayores y mejores estilos de vida, dándose dentro de éste marco el Teletrabajo. El desarrollo tecnológico permite hoy un nuevo concepto de las oficinas y aun de las empresas, permitiendo optar por oficinas o empresas virtuales, no ligadas a un espacio físico sino conformadas por una red de relaciones telemáticas. Empresas susceptibles de generar elevadas facturaciones con una dotación escasísima de personal fijo.Universidad Estatal a Distancia de Costa Ric

Is thyroid nodule location associated with malignancy risk?

PURPOSE: Nodules located in the upper pole of the thyroid may carry a greater risk for malignancy than those in the lower pole. We conducted a study to analyze the risk of malignancy of nodules depending on location. METHODS: The records of patients undergoing thyroid-nodule fine-needle aspiration cytology (FNAC) at an academic thyroid cancer unit were prospectively collected. The nodules were considered benign in cases of a benign histology or cytology report, and malignant in cases of malignant histology. Pathological findings were analyzed based on the anatomical location of the nodules, which were also scored according to five ultrasonographic classification systems. RESULTS: Between November 1, 2015 and May 30, 2018, 832 nodules underwent FNAC, of which 557 had a definitive diagnosis. The prevalence of malignancy was not significantly different in the isthmus, right, or left lobe. Among the 227 nodules that had a precise longitudinal location noted (from 219 patients [155 females], aged 56.2±14.0 years), malignancy was more frequent in the middle lobe (13.2%; odds ratio [OR], 9.74; 95% confidence interval [CI], 1.95 to 48.59). This figure was confirmed in multivariate analyses that took into account nodule composition and the Thyroid Imaging, Reporting, and Data System (TIRADS) classification. Using the American College of Radiologists TIRADS, the upper pole location also demonstrated a slightly significant association with malignancy (OR, 6.92; 95% CI, 1.02 to 46.90; P=0.047). CONCLUSION: The risk of thyroid malignancy was found to be significantly higher for mid-lobar nodules. This observation was confirmed when suspicious ultrasonographic features were included in a multivariate model, suggesting that the longitudinal location in the lobe may be a risk factor independently of ultrasonographic appearance

Carbon Ion Radiobiology

Radiotherapy using accelerated charged particles is rapidly growing worldwide. About 85% of the cancer patients receiving particle therapy are irradiated with protons, which have physical advantages compared to X-rays but a similar biological response. In addition to the ballistic advantages, heavy ions present specific radiobiological features that can make them attractive for treating radioresistant, hypoxic tumors. An ideal heavy ion should have lower toxicity in the entrance channel (normal tissue) and be exquisitely effective in the target region (tumor). Carbon ions have been chosen because they represent the best combination in this direction. Normal tissue toxicities and second cancer risk are similar to those observed in conventional radiotherapy. In the target region, they have increased relative biological effectiveness and a reduced oxygen enhancement ratio compared to X-rays. Some radiobiological properties of densely ionizing carbon ions are so distinct from X-rays and protons that they can be considered as a different “drug” in oncology, and may elicit favorable responses such as an increased immune response and reduced angiogenesis and metastatic potential. The radiobiological properties of carbon ions should guide patient selection and treatment protocols to achieve optimal clinical results

Dose Limits and Countermeasures for Mitigating Radiation Risk in Moon and Mars Exploration

After decades of research on low-Earth orbit, national space agencies and private entrepreneurs are investing in exploration of the Solar system. The main health risk for human space exploration is late toxicity caused by exposure to cosmic rays. On Earth, the exposure of radiation workers is regulated by dose limits and mitigated by shielding and reducing exposure times. For space travel, different international space agencies adopt different limits, recently modified as reviewed in this paper. Shielding and reduced transit time are currently the only practical solutions to maintain acceptable risks in deep space missions