FLT-PET in previously untreated patients with low-grade glioma can predict their overall survival

BACKGROUND: Low-grade gliomas (LGG) of the brain have an uncertain prognosis, as many of them show continuous growth or upgrade over the course of time. We retrospectively investigated the role of positron emission tomography with 3’-deoxy-3’-[18F]fluorothymidine (FLT-PET) in the prediction of overall survival and event free survival in patients with untreated LGG. No such information is yet available in the literature. MATERIAL AND METHODS: Forty-one patients with previously untreated LGG underwent 55 FLT-PET investigations during their follow-up because of subjective complaints, objective worsening of clinical conditions, equivocal findings or progression on magnetic resonance imaging. The time interval before referral for neurosurgical or radiation treatment was considered to be event free survival, the interval until death as overall survival, respectively. Standardized uptake values (SUV) were measured, and a 3-point scale of subjective assessment was also applied. ROC analysis was used to define cut-off values. The log rank test was used for comparison of Kaplan-Meier survival curves. RESULTS: Eight patients (a total of 9 FLT-PET studies performed) died during follow-up. Progression leading to referral to therapy was recorded in 24 patients (a total of 33 FLT-PET studies). With a cut-off value of SUVmean = 0.236, a median overall survival of 1.007 days was observed in the test positive subgroup while median overall survival for the test negative subgroup was not achieved (p = 0.0002), hazard ratio = 17.6. Subjective assessment resulted in hazard ratio 11.5 (p = 0.0001). Only marginal significance (p=0.0562) was achieved in prediction of event free survival. CONCLUSIONS: Increased FLT uptake in previously untreated patients with LGG is a strong predictor of overall survival. On the other hand, prediction of event free survival was not successful in our cohort, probably because of high prevalence of patients who needed treatment due to symptoms caused by a space-occupying lesion without respect to the proliferative activity of the tumour

Whole-body single-cell sequencing reveals transcriptional domains in the annelid larval body.

Animal bodies comprise diverse arrays of cells. To characterise cellular identities across an entire body, we have compared the transcriptomes of single cells randomly picked from dissociated whole larvae of the marine annelid Platynereis dumerilii. We identify five transcriptionally distinct groups of differentiated cells, each expressing a unique set of transcription factors and effector genes that implement cellular phenotypes. Spatial mapping of cells into a cellular expression atlas, and wholemount in situ hybridisation of group-specific genes reveals spatially coherent transcriptional domains in the larval body, comprising e.g. apical sensory-neurosecretory cells vs. neural/epidermal surface cells. These domains represent new, basic subdivisions of the annelid body based entirely on differential gene expression, and are composed of multiple, transcriptionally similar cell types. They do not represent clonal domains, as revealed by developmental lineage analysis. We propose that the transcriptional domains that subdivide the annelid larval body represent families of related cell types that have arisen by evolutionary diversification. Their possible evolutionary conservation makes them a promising tool for evo-devo research. (167/250).KA and JM were supported by the Marie Curie COFUND programme from the European Commission and by EMBL core funding. NE, PC, VB, and DA were supported by core funding from EMBL. KA, HMV, PYB, PV were supported by the Advanced grant “Brain Evo-Devo” from the European Research Council. JCM was supported by core funding from EMBL and Cancer Research UK

Adrenomedullin and tumour microenvironment

Adrenomedullin (AM) is a regulatory peptide whose involvement in tumour progression is becoming more relevant with recent studies. AM is produced and secreted by the tumour cells but also by numerous stromal cells including macrophages, mast cells, endothelial cells, and vascular smooth muscle cells. Most cancer patients present high levels of circulating AM and in some cases these higher levels correlate with a worst prognosis. In some cases it has been shown that the high AM levels return to normal following surgical removal of the tumour, thus indicating the tumour as the source of this excessive production of AM. Expression of this peptide is a good investment for the tumour cell since AM acts as an autocrine/paracrine growth factor, prevents apoptosis-mediated cell death, increases tumour cell motility and metastasis, induces angiogenesis, and blocks immunosurveillance by inhibiting the immune system. In addition, AM expression gets rapidly activated by hypoxia through a HIF-1α mediated mechanism, thus characterizing AM as a major survival factor for tumour cells. Accordingly, a number of studies have shown that inhibition of this peptide or its receptors results in a significant reduction in tumour progression. In conclusion, AM is a great target for drug development and new drugs interfering with this system are being developed

Root anatomy of three carnivorous plant species

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Chemistry of Molten Salt Reactor Fuel Salt Candidates

Molten salt reactor (MSR) concepts are based on using a molten salt mixture as a primary nuclear reactor coolant, while the fuel can be either directly dissolved in the coolant or can be solid. MSRs can be operated with (epi)thermal or fast neutron spectra, as simple convertors or breeder reactors utilising, e.g., the 232Th-233U cycle, but also as accelerator-driven sub-critical reactors or transuranium elements (TRU) burners. The main advantages of the MSRs using a liquid molten salt fuel resides in the enhanced safety features such as a large negative temperature coefficient of reactivity due to a high thermal expansion, low atmospheric pressure in the core during the operation and no need of transport and fabrication of new fuel elements in the case of closed fuel cycle option. In addition, the liquid fuel brings possibility of continuous fission-product removal via physical and pyrochemical processes which brings flexibility in the fuel cycle. In the last years, development of MSR technology is on the increase in many countries and since 2002, the MSR concept is included to the Generation IV initiative. Since 2001, the European Commission (EC) carries on coordinated R&D activities on the MSR concept within the EC/EURATOM framework programmes. Several projects have been funded exploring the feasibility and safety of the Molten Salt Fast Reactor (MSFR) concept studied in Europe. MSFR is based on a non-moderated epi-thermal neutron spectrum with its fuel dissolved in a fluoride molten salt carrier and utilising a closed thorium fuel cycle. Basic thermodynamic and electrochemical data of pure actinide fluorides and their mixtures are required for the design and safety assessment of any presently studied molten salt reactor concept based on molten fluoride salt fuel. The present work is summarising the recent research in this field carried out at Joint Research Centre (JRC) of the European Commission. It is particularly focused on the synthesis and characterisation of pure actinide fluorides UF4, ThF4 and PuF3 needed for the experimental assessment of the thermodynamic properties of the MSR fuel salt candidates. In addition, the recent achievements of these studies are presented, e.g., re-determination of the UF4 melting point and measurement of the novel thermodynamic data of PuF3-LiF system.JRC.G.I.3-Nuclear Fuel Safet