Le devenir-Dieu des personnages kazantzakiens : l'oeuvre de Kazantzaki à la lumière de la philosophie bergsonienne

In Creative Evolution, Bergson has put forward the idea of a super-man, who would continue the effort that life has fixed in the evolution of species, and would rise toward a constantly actualized divine freedom. The work of Kazantzaki appears in our study as a creation where the super-man, whose story must remain singular, is materialized. The bergsonian notion of duration used as a method to approach the text, reveals within the text a particular way of thinking the creation in the work and in oneself. It is presented as the continuous fixation of a maturation, slowed by material forms, that can not contain it anymore : in particular the language and the intellectual, and not sufficiently intuitive, vision of the world. Inspired by the bergsonian philosophy, Kazantzaki tries to imprint the spirit’s ascending mobility to his characters, by liberating them from all those closures that divide up the moving reality and reduce the power of the soul. We oppose to the idea of a character emerging like a creation ex nihilo, the bergsonian idea of novelty which would result from an effort testing the writer and the character’s freedom, and which would concentrate in the case of the super-man the human and pre-human history. Following those two lines of evolution which are particular to Bergson and Kazantzaki, each one in his area and confronted to different impediments, we see them converging by the similar movement of their thought and interrogate finally one type of man’s effort : the mystic.Dans l’Évolution créatrice, Bergson émet l’idée d’un sur-homme, individu qui prolongerait l’effort que la vie a fixé dans l’évolution des espèces, et qui s’élèverait vers une liberté divine incessamment actualisée. L’œuvre littéraire de Kazantzaki apparait dans notre étude comme le lieu de matérialisation de ce sur-homme à l’histoire singulière. La notion bergsonienne de durée, utilisée comme méthode d’approche du texte, révèle à l’intérieur des textes de l’auteur grec une façon particulière de penser la création, dans l’œuvre et en soi. Celle-ci est présentée comme la fixation progressive d’une maturation de l’auteur, ralentie par des formes matérielles qui ne la contiennent plus : en particulier celle du langage et d’une perception trop intellectuelle, et pas assez intuitive, du monde. Inspiré par le modèle bergsonien, Kazantzaki essaie d’imprimer la mobilité ascendante de l’esprit à ses personnages en les affranchissant au fur et à mesure de leur montée, de toutes ces clôtures qui morcellent la réalité fluente et indivisible et réduisent la puissance de l’âme. A l’idée d’un personnage émergeant comme une création ex nihilo, on substitue l’idée bergsonienne d’une nouveauté apportée par un effort éprouvant la liberté de l’individu, celle de l’écrivain et celle du personnage, qui concentrerait dans le cas du sur-homme l’histoire humaine et pré-humaine. Suivant ainsi ces deux lignes d’évolution propres à Kazantzaki et à Bergson, chacun dans leur domaine, confrontés à différents obstacles, nous les voyons converger par le mouvement similaire de leur pensée et interroger finalement l’effort d’un même type d’homme, le mystique

Robotic image-guided reirradiation of lateral pelvic recurrences: preliminary results

<p>Abstract</p> <p>Background</p> <p>The first-line treatment of a pelvic recurrence in a previously irradiated area is surgery. Unfortunately, few patients are deemed operable, often due to the location of the recurrence, usually too close to the iliac vessels, or the associated surgical morbidity. The objective of this study is to test the viability of robotic image-guided radiotherapy as an alternative treatment in inoperable cases.</p> <p>Methods</p> <p>Sixteen patients previously treated with radiotherapy were reirradiated with CyberKnife^®for lateral pelvic lesions. Recurrences of primary rectal cancer (4 patients), anal canal (6), uterine cervix cancer (4), endometrial cancer (1), and bladder carcinoma (1) were treated. The median dose of the previous treatment was 45 Gy (EqD2 range: 20 to 96 Gy). A total dose of 36 Gy in six fractions was delivered with the CyberKnife over three weeks. The responses were evaluated according to RECIST criteria.</p> <p>Results</p> <p>Median follow-up was 10.6 months (1.9 to 20.5 months). The actuarial local control rate was 51.4% at one year. Median disease-free survival was 8.3 months after CyberKnife treatment. The actuarial one-year survival rate was 46%. Acute tolerance was limited to digestive grade 1 and 2 toxicities.</p> <p>Conclusions</p> <p>Robotic stereotactic radiotherapy can offer a short and well-tolerated treatment for lateral pelvic recurrences in previously irradiated areas in patients otherwise not treatable. Efficacy and toxicity need to be evaluated over the long term, but initial results are encouraging.</p

The impact of a radiologist-led workshop on MRI target volume delineation for radiotherapy

Introduction: Magnetic resonance imaging (MRI) is increasingly used for target volume delineation in radiotherapy due to its superior soft tissue visualisation compared to computed tomography (CT). The aim of this study was to assess the impact of a radiologist-led workshop on inter-observer variability in volume delineation on MRI. Methods: Data from three separate studies evaluating the impact of MRI in lung, breast and cervix were collated. At pre-workshop evaluation, observers involved in each clinical site were instructed to delineate specified volumes. Radiologists specialising in each cancer site conducted an interactive workshop on interpretation of images and anatomy for each clinical site. At post-workshop evaluation, observers repeated delineation a minimum of 2 weeks after the workshops. Inter-observer variability was evaluated using dice similarity coefficient (DSC) and volume similarity (VOLSIM) index comparing reference and observer volumes. Results: Post-workshop primary gross tumour volumes (GTV) were smaller than pre-workshop volumes for lung with a mean percentage reduction of 10.4%. Breast clinical target volumes (CTV) were similar but seroma volumes were smaller post-workshop on both supine (65% reduction) and prone MRI (73% reduction). Based on DSC scores, improvement in inter-observer variability was seen for the seroma cavity volume on prone MRI with a reduction in DSC score range from 0.4-0.8 to 0.7-0.9. Breast CTV demonstrated good inter-observer variability scores (mean DSC 0.9) for both pre- and post-workshop. Post-workshop observer delineated cervix GTV was smaller than pre-workshop by 26.9%. Conclusion: A radiologist-led workshop did not significantly reduce inter-observer variability in volume delineation for the three clinical sites. However, some improvement was noted in delineation of breast CTV, seroma volumes and cervix GTV

Differential changes in gene expression in human neutrophils following TNF-α stimulation: Up-regulation of anti-apoptotic proteins and down-regulation of proteins involved in death receptor signaling.

Responses of human neutrophils to TNF-α are complex and multifactorial. Exposure of human neutrophils to TNF-α in vitro primes the respiratory burst, delays apoptosis and induces the expression of several genes including chemokines, and TNF-α itself. This study aimed to determine the impact of TNF-α exposure on the expression of neutrophil genes and proteins that regulate apoptosis. Quantitative PCR and RNA-Seq, identified changes in expression of several apoptosis regulating genes in response to TNF-α exposure. Up-regulated genes included TNF-α itself, and several anti-apoptotic genes, including BCL2A1, CFLAR (cFLIP) and TNFAIP3, whose mRNA levels increased above control values by between 4-20 fold (n = 3, P < 0.05). In contrast, the expression of pro-apoptotic genes, including CASP8, FADD and TNFRSF1A and TNFRSF1B, were significantly down-regulated following TNF-α treatment. These changes in mRNA levels were paralleled by decreases in protein levels of caspases 8 and 10, TRADD, FADD, TNFRSF1A and TNFRSF1B, and increased cFLIP protein levels, as detected by western blotting. These data indicate that when neutrophils are triggered by TNF-α exposure, they undergo molecular changes in transcriptional expression to up-regulate expression of specific anti-apoptotic proteins and concomitantly decrease expression of specific proteins involved in death receptor signaling which will alter their function in TNF-α rich environments

Conformity analysis to demonstrate reproducibility of target volumes for Margin-Intense Stereotactic Radiotherapy for borderline-resectable pancreatic cancer.

Margin-directed neoadjuvant radiotherapy for borderline-resectable pancreatic cancer (BRPC) aims to facilitate clear surgical margins. A systematic method was developed for definition of a boost target volume prior to a formal phase-I study.Reference structures were defined by two oncologists and one radiologist, target structures were submitted by eight oncologist investigators and compared using conformity indices. Resultant risk of duodenal bleed (NTCP) was modelled.For GTV, reference volume was 2.1cm(3) and investigator mean was 6.03cm(3) (95% CI 3.92-8.13cm(3)), for boost volume 1.1cm(3) and 1.25cm(3) (1.02-1.48cm(3)). Mean Dice conformity coefficient for GTV was 0.47 (0.38-0.56), and for boost volume was significantly higher at 0.61 (0.52-0.70, p=0.01). Discordance index (DI) for GTV was 0.65 (0.56-0.75) and for boost volume was significantly lower at 0.39 (0.28-0.49, p=0.001). NTCP using reference contours was 2.95%, with mean for investigator contour plans 3.93% (3.63-4.22%). Correlations were seen between NTCP and GTV volume (p=0.02) and NTCP and DI (correlation coefficient 0.83 (0.29-0.97), p=0.01).Better conformity with reference was shown for boost volume compared with GTV. Investigator GTV volumes were larger than reference, had higher DI scores and modelled toxicity risk. A consistent method of target structure definition for margin-directed pancreatic radiotherapy is demonstrated

Initial Results from the Royal College of Radiologists' UK National Audit of Anal Cancer Radiotherapy 2015

Aims: UK guidance was recently developed for the treatment of anal cancer using intensity-modulated radiotherapy (IMRT). We audited the current use of radiotherapy in UK cancer centres for the treatment of anal cancer against such guidance. We describe the acute toxicity of IMRT in comparison with patient population in the audit treated with two-phase conformal radiotherapy and the previous published data from two-phase conformal radiotherapy, in the UK ACT2 trial. Materials and methods: A Royal College of Radiologists' prospective national audit of patients treated with radiotherapy in UK cancer centres was carried out over a 6 month period between February and July 2015. Results: Two hundred and forty-two cases were received from 40/56 cancer centres (71%). In total, 231 (95%) underwent full dose radiotherapy with prophylactic nodal irradiation. Of these, 180 (78%) received IMRT or equivalent, 52 (22%) two-phase conformal (ACT2) technique. The number of interruptions in radiotherapy treatment in the ACT2 trial was 15%. Interruptions were noted in 7% (95% confidence interval 0–14%) of courses receiving two-phase conformal and 4% (95% confidence interval 1–7%) of those receiving IMRT. The percentage of patients completing the planned radiotherapy dose, irrelevant of gaps, was 90% (95% confidence interval 82–98%) and 96% (95% confidence interval 93–99%), in two-phase conformal and IMRT respectively. The toxicity reported in the ACT2 trial, in patients receiving two-phase conformal in the audit and in patients receiving IMRT in the audit was: any toxic effect 71%, 54%, 48%, non-haematological 62%, 49%, 40% and haematological 26%, 13%, 18%, respectively. Conclusions: IMRT implementation for anal cancer is well underway in the UK with most patients receiving IMRT delivery, although its usage is not yet universal. This audit confirms that IMRT results in reduced acute toxicity and minimised treatment interruptions in comparison with previous two-phase conformal techniques

Adjuvant radiation therapy in metastatic lymph nodes from melanoma

<p>Abstract</p> <p>Purpose</p> <p>To analyze the outcome after adjuvant radiation therapy with standard fractionation regimen in metastatic lymph nodes (LN) from cutaneous melanoma.</p> <p>Patients and methods</p> <p>86 successive patients (57 men) were treated for locally advanced melanoma in our institution. 60 patients (69%) underwent LN dissection followed by radiation therapy (RT), while 26 patients (31%) had no radiotherapy.</p> <p>Results</p> <p>The median number of resected LN was 12 (1 to 36) with 2 metastases (1 to 28). Median survival after the first relapse was 31.8 months. Extracapsular extension was a significant prognostic factor for regional control (p = 0.019). Median total dose was 50 Gy (30 to 70 Gy). A standard fractionation regimen was used (2 Gy/fraction). Median number of fractions was 25 (10 to 44 fractions). Patients were treated with five fractions/week. Patients with extracapsular extension treated with surgery followed by RT (total dose ≥50 Gy) had a better regional control than patients treated by surgery followed by RT with a total dose <50 Gy (80% vs. 35% at 5-year follow-up; p = 0.004).</p> <p>Conclusion</p> <p>Adjuvant radiotherapy was able to increase regional control in targeted sub-population (LN with extracapsular extension).</p

Metabolic and Innate Immune Cues Merge into a Specific Inflammatory Response via the UPR

Erratum in : Metabolic and Innate Immune Cues Merge into a Specific Inflammatory Response via the UPR. [Cell. 2019]International audienceInnate immune responses are intricately linked with intracellular metabolism of myeloid cells. Toll-likereceptor (TLR) stimulation shifts intracellular metabolism toward glycolysis, while anti-inflammatorysignals depend on enhanced mitochondrial respiration. How exogenous metabolic signals affect theimmune response is unknown. We demonstrate that TLR-dependent responses of dendritic cells (DC)are exacerbated by a high fatty acid (FA) metabolic environment. FA suppress the TLR-inducedhexokinase activity and perturb tricarboxylic acid cycle metabolism. These metabolic changesenhance mitochondrial reactive oxygen species (mtROS) production and, in turn, the unfolded proteinresponse (UPR) leading to a distinct transcriptomic signature, with IL-23 as hallmark. Interestingly,chemical or genetic suppression of glycolysis was sufficient to induce this specific immune response.Conversely, reducing mtROS production or DC-specific deficiency in XBP1 attenuated IL-23expression and skin inflammation in an IL-23-dependent model of psoriasis. Thus, fine-tuning of innateimmunity depends on optimization of metabolic demands and minimization of mtROS-induced UPR

Innate immunity based cancer immunotherapy: B16-F10 murine melanoma model

Abstract Background Using killed microorganisms or their parts to stimulate immunity for cancer treatment dates back to the end of 19th century. Since then, it undergone considerable development. Our novel approach binds ligands to the tumor cell surface, which stimulates tumor phagocytosis. The therapeutic effect is further amplified by simultaneous application of agonists of Toll-like receptors. We searched for ligands that induce both a strong therapeutic effect and are safe for humans. Methods B16-F10 murine melanoma model was used. For the stimulation of phagocytosis, mannan or N-formyl-methionyl-leucyl-phenylalanine, was covalently bound to tumor cells or attached using hydrophobic anchor. The following agonists of Toll-like receptors were studied: monophosphoryl lipid A (MPLA), imiquimod (R-837), resiquimod (R-848), poly(I:C), and heat killed Listeria monocytogenes. Results R-848 proved to be the most suitable Toll-like receptor agonist for our novel immunotherapeutic approach. In combination with covalently bound mannan, R-848 significantly reduced tumor growth. Adding poly(I:C) and L. monocytogenes resulted in complete recovery in 83% of mice and in their protection from the re-transplantation of melanoma cells. Conclusion An efficient cancer treatment results from the combination of Toll-like receptor agonists and phagocytosis stimulating ligands bound to the tumor cells.http://deepblue.lib.umich.edu/bitstream/2027.42/134739/1/12885_2016_Article_2982.pd