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The discharged pharmaceutical compounds in water have created environmental problems due to their harmful potential at low concentrations. Finding an environmentally friendly treatment process is a real challenge to avoid water contamination. Heterogeneous photocatalysis, can be used for the degradation of organic compounds, but each pollutant must be studied. The aim of this study was to explore the potential of TiO2 Degusa commercial photocatalysis for elimination of levetiracetam (Lev), an anticonvulsant used to treat certain types of seizures. Tests were carried out in a batch reactor, mechanically stirred, with external irradiation using UVA light, ambient temperature, at natural pH of solution. UV irradiation was generated by two Philips PL-S lamps (9W). The experiments were performed for a catalyst loading of 1 g/L and at an initial concentration of Lev in the range of 5 - 25 mg/L. After adsorption-desorption equilibrium, all experiments being performed for an irradiation time of 140 min. Samples were taken at regular time intervals, filtered and the residual concentration of pollutant was measured (liquid chromatography - HPLC, using a Waters 600 PDA system) to determine the photodegradation efficiency. The influence of different parameters was investigated and in optimal conditions a photodegradation yield of 99% was achieved.

In the present study, the photocatalytic degradation of methylene blue (MB), using TiO2-Ag synthesized by sol-gel method, as a catalyst under UV light, was studied. The samples synthesized were characterized by SEM, EDAX, FTIR, XRD and TEM. The average size of the particles was 10 nm. Tests were carried out in a batch reactor, magnetically stirred, with external irradiation using UVB lamp of Hg - 18 W, having intensity of incident radiation 2.1 W/m2. The effects of some parameters, such as catalyst dosage, pH and initial acetone concentration were investigated. Results showed that the optimal catalyst concentration was 0.03 g/L, at concentration of MB solution of 1.25∙10-5 mol/L. The mechanism of degradation of MB in presence of acetone was proposed. The results obtained in this work are very promising, using TiO2-Ag as photocatalyst, especially in presence of acetone as photosensitizer, when degradation percentage increases from 60% for TiO2 without Ag to 92.38% for TiO2-Ag and 0.1% acetone and 97.25% for 0.2% acetone. The photocatalysis followed pseudo-first order reaction kinetic behaviour, with the rate constants ranging from 0.0009 to 0.11 min-1 under the studied conditions. The reaction rate depends nonlinear of acetone concentration, the constants of polynomial function being calculated.

Background BRAF mutations occurring in 1%–5% of patients with non-small-cell lung cancer (NSCLC) are therapeutic targets for these cancers but the impact of the exact mutation on clinical activity is unclear. The French National Cancer Institute (INCA) launched the AcSe vemurafenib trial to assess the efficacy and safety of vemurafenib in cancers with various BRAF mutations. We herein report the results of the NSCLC cohort. Patients and methods Tumour samples were screened for BRAF mutations in INCA-certified molecular genetic centres. Patients with BRAF-mutated tumours progressing after ≥1 line of treatment were proposed vemurafenib 960 mg twice daily. Between October 2014 and July 2018, 118 patients were enrolled in the NSCLC cohort. The primary outcome was the objective response rate (ORR) assessed every 8 weeks (RECIST v1.1). A sequential Bayesian approach was planned with an inefficacy bound of 10% for ORR. If no early stopping occurred, the treatment was of interest if the estimated ORR was ≥30% with a 90% probability. Secondary outcomes were tolerance, response duration, progression-free survival (PFS), and overall survival (OS). Results Of the 118 patients enrolled, 101 presented with a BRAFV600 mutation and 17 with BRAFnonV600 mutations; the median follow-up was 23.9 months. In the BRAFnonV600 cohort, no objective response was observed and this cohort was stopped. In the BRAFV600 cohort, 43/96 patients had objective responses. The mean Bayesian estimated success rate was 44.9% [95% confidence intervals (CI) 35.2%–54.8%]. The ORR had a 99.9% probability of being ≥30%. Median response duration was 6.4 months, median PFS was 5.2 months (95% CI 3.8–6.8), and OS was 10 months (95% CI 6.8–15.7). The vemurafenib safety profile was consistent with previous publications. Conclusion Routine biomarker screening of NSCLC should include BRAFV600 mutations. Vemurafenib monotherapy is effective for treating patients with BRAFV600-mutated NSCLC but not those with BRAFnonV600 mutations. Trial registration ClinicalTrials.gov identifier: NCT02304809.

Background: Bevacizumab is approved in combination with chemotherapy for the treatment of ovarian cancer, either in first-line therapy or for patients with recurrent disease not previously treated with the same drug. We aimed to test the value of continuing bevacizumab beyond progression after first-line treatment with the same drug. Methods: In our open-label, randomised, phase 3 trial done at 82 sites in four countries, we enrolled women (aged ≥18 years) who had previously received first-line platinum-based therapy including bevacizumab, and had recurrent (≥6 months since last platinum dose), International Federation of Gynaecology and Obstetrics stage IIIB–IV ovarian cancer with an Eastern Cooperative Oncology Group performance status 0–2. Patients were randomly assigned (1:1) to receive a carboplatin-based doublet intravenously (carboplatin area under the concentration curve [AUC] 5 on day 1 plus paclitaxel 175 mg/m2 on day 1, every 21 days; carboplatin AUC 4 on day 1 plus gemcitabine 1000 mg/m2 on days 1 and 8, every 21 days; or carboplatin AUC 5 on day 1 plus pegylated liposomal doxorubicin 30 mg/m2 on day 1, every 28 days), or a carboplatin-based doublet plus bevacizumab (10 mg/kg intravenous every 14 days combined with pegylated liposomal doxorubicin–carboplatin, or 15 mg/kg every 21 days combined with gemcitabine–carboplatin or paclitaxel–carboplatin). Evaluable disease according to RECIST 1.1 guidelines was required before randomisation. Randomisation was done through the trial website with a minimisation procedure, stratified by centre, time of recurrence, performance status, and type of second-line chemotherapy. The primary endpoint was investigator-assessed progression-free survival, analysed on an intention-to-treat basis. Safety was assessed in all participants who received at least one dose. This trial is registered with ClinicalTrials.gov, NCT01802749 and EudraCT 2012-004362-17. Findings: Between Dec 6, 2013, and Nov 11, 2016, 406 patients were recruited (203 [50%] assigned to the bevacizumab group and 203 [50%] to the standard chemotherapy group). 130 patients (64%) in the bevacizumab group and 131 (65%) in the standard chemotherapy group had progressed after receiving a last dose of platinum more than 12 months before, and 146 patients (72%) in the bevacizumab group and 147 (72%) in the standard chemotherapy group had progressed after completion of first-line bevacizumab maintenance. 161 participants (79%) progressed in the standard chemotherapy group, as did 143 (70%) in the bevacizumab group. Median progression-free survival was 8·8 months (95% CI 8·4–9·3) in the standard chemotherapy group and 11·8 months (10·8–12·9) in the bevacizumab group (hazard ratio 0·51, 95% CI 0·41–0·65; log-rank p

Objectives The aim was to assess the incidence of sink contamination by multidrug-resistant (MDR) Pseudomonas aeruginosa and Enterobacteriaceae, risk factors for sink contamination and splashing, and their association with clinical infections in the intensive care setting. Methods A prospective French multicentre study (1 January to 30 May 2020) including in each intensive care unit (ICU) a point-prevalence study of sink contamination, a questionnaire of risk factors for sink contamination (sink use, disinfection procedure) and splashing (visible plashes, distance and barrier between sink and bed), and a 3-month prospective infection survey. Results Seventy-three ICUs participated in the study. In total, 50.9% (606/1191) of the sinks were contaminated by MDR bacteria: 41.0% (110/268) of the sinks used only for handwashing, 55.3% (510/923) of those used for waste disposal, 23.0% (62/269) of sinks daily bleached, 59.1% (126/213) of those daily exposed to quaternary ammonium compounds (QACs) and 62.0% (285/460) of those untreated; 459 sinks (38.5%) showed visible splashes and 30.5% (363/1191) were close to the bed ( Discussion Our data showed frequent and multifactorial infectious risks associated with contaminated sinks in ICUs.

The busbars for the HL-LHC magnets are made of Nb-Ti/Cu conductor, the insulation system, and the auxiliary equipment to align the busbars with respect to the magnet coldmasses. This paper presents design options concerning the integration of the busbars inside the coldmass with a fixed point, and a reinforced insulation system for the flexible busbar part using thin PEEK tubes. Prototype splices for interconnecting Nb3Sn and Nb-Ti Rutherford cables, and round and flat 18 kA Nb-Ti cable have been produced and first test results are presented.

Introduction/Background The rare vaginal and vulvar cancers are considered to be histologically similar to cervical squamous cell carcinoma. However, mutational landscape differences between them are unclear. In the time of precision medicine and immunotherapy, a personalized therapy approach based on a detailed biological characterization of each tumor entity should be considered. This study aimed to identify differences and specific genetic alterations in vaginal and vulvar compared to cervical squamous cell carcinoma. Methodology Using next generation sequencing (NGS), both somatic and germline exome sequencing of vulvar (n=11), vaginal (n=9) and cervical cancer (n=11) were analyzed. To determine a potential sensitivity to immunotherapy, we studied tumor mutation burden, ratio indels, TCR clonality, neopeptides, Alexandrov9s signatures, and copy number variation. Additionally a signaling pathway analysis was performed applying 2 different approaches (NCI and KEGG). Results No significant differences were seen in the respective immunologic predictive biomarkers comparing the three tumor entities. The signaling pathway analysis revealed an alteration of antigen processing and presentation pathways in vulvar and vaginal cancer compared to cervical cancer (77 genes). Moreover, an activation of Notch signaling was found in vulvar and vaginal tumors. Vulvar and vaginal cancer reveal a comparable mutational landscape in the analyzed genes. Conclusion NGS determines a potential immune evasion strategy of vulvar and vaginal tumors related to an alteration of antigen presentation. Our findings suggest that immunotherapy might be less efficient compared to cervical cancer. Targeting Notch and mTOR pathway may be a promising therapy approach in these rare tumors. Disclosure Nothing to disclose

BRAF mutations occurring in 1%-5% of patients with non-small-cell lung cancer (NSCLC) are therapeutic targets for these cancers but the impact of the exact mutation on clinical activity is unclear. The French National Cancer Institute (INCA) launched the AcSé vemurafenib trial to assess the efficacy and safety of vemurafenib in cancers with various BRAF mutations. We herein report the results of the NSCLC cohort.Tumour samples were screened for BRAF mutations in INCA-certified molecular genetic centres. Patients with BRAF-mutated tumours progressing after ≥1 line of treatment were proposed vemurafenib 960 mg twice daily. Between October 2014 and July 2018, 118 patients were enrolled in the NSCLC cohort. The primary outcome was the objective response rate (ORR) assessed every 8 weeks (RECIST v1.1). A sequential Bayesian approach was planned with an inefficacy bound of 10% for ORR. If no early stopping occurred, the treatment was of interest if the estimated ORR was ≥30% with a 90% probability. Secondary outcomes were tolerance, response duration, progression-free survival (PFS), and overall survival (OS).Of the 118 patients enrolled, 101 presented with a BRAFRoutine biomarker screening of NSCLC should include BRAFClinicalTrials.gov identifier: NCT02304809.

Muscle regeneration after injury (as irradiation) is of great importance. However, the molecular and cellular mechanisms are still unclear. Cytokines are believed to play fundamental role in the different stages of muscle regeneration. They are secreted by many cell populations, but the predominant producers are macrophages and helper T cells. On the other hand, it has been shown that adipose tissue derived stromal/stem cell (ASC) injection could improve muscle regeneration. Stem cells probably induce the coordinated modulations of gene expression in different macrophage cells. Therefore, we investigated the patterns and timing of changes in gene expression of different cytokines occurring upon stem cells loading. Muscle regeneration was studied in an irradiated muscle of minipig animal model in presence or absence of ASC treatment (irradiated and treated with ASCs, IRR+ASC; irradiated not-treated with ASCs, IRR; and non-irradiated no-IRR). We characterized macrophage populations by immunolabeling in the different conditions. In our study, we found mostly M2 and a few M1 macrophages in the IRR+ASC samples. However, only few M2b macrophages were noticed in the IRR muscles. In addition, we found intensive fibrosis in the IRR samples. With in situ hybridization and immunolabeling, we analyzed the cytokine expression of the different macrophages and we showed that M2d macrophage are the most abundant in the IRR+ASC samples. By in situ hybridization, strong expression of the transforming growth factor β (TGF-β) was observed in the IRR+ASC but very week in the IRR samples. But when we analyzed TGF-β level with immunolabeling the expression was very different: many M2 macrophages showed week expression in IRR+ASC and few cells expressing stronger level in IRR muscles. Therefore, we investigated the MMP expressions in the different muscles. Our data showed that the M2 macrophages of the IRR+ASC muscle expressed MMP2 proteins. Our working hypothesis is that MMP2 expression of the M2 macrophages can decrease fibrosis in the IRR+ASC muscle by capturing TGF-β., {"references":["Arnold L. et al., (2007) Inflammatory monocytes recruited after skeletal muscle injury switch into anti-inflammatory macrophages to support myogenesis. J Exp Med. 204: 1057–1069.","Bornemann A. et al., (1999) Satellite Cells as Players and Targets in Normal and Diseased Muscle. Neuropediatrics 30: 167-175","Cantini M. et al., (1994) Macrophages regulate proliferation and differentiation of satellite cells. Biochem Biophys Res Commun. 202: 1688-1696.","Cantini M. and Carraro U., (1995) Macrophage-released factor stimulates selectively myogenic cells in primary muscle culture. J Neuropathol Exp Neurol. 54: 121-8.","Chen L. et al., (2008) Paracrine Factors of Mesenchymal Stem Cells Recruit Macrophages and Endothelial Lineage Cells and Enhance Wound Healing. Plos ONE 3: e1886.","Delaney K. et al., (2016) The role of TGF-1 during skeletal muscle regeneration. Cell Biol Int doi: 10/1002/cbin.10725.","Ferrante C.J. And Leibovich (2012) Regulation of Macrophage Polarization and Wound Healing. Adv In Wound Care 1: 10-16.","Liu X. et al., (2017) Macrophage depletion impairs skeletal muscle regeneration: The roles of regulatory factors for muscle regeneration. Cell Biol Int. 3: 228-238.","Martinez F.O. and Gordon S., (2014) The M1 and M2 paradigm of macrophage activation: time for reassessment. F1000Prime Rep. Mar 3;6:13. doi: 10.12703/P6-13. eCollection 2014.\n[10]\tMu X. et al., (2010) Relaxin Regulates MMP Expression and Promotes Satellite Cell Mobilization During Muscle Healing in Both Young and Aged Mice. Am J Pathol. 177: 2399–2410. \n[11]\tPhilippou A. et al., (2012) Cytokines in muscle damage. Adv Clin Chem. 58: 49-87.\n[12]\tRiccobono D.et al., (2016) Contribution of INTRAMUSCULAR Autologous Adipose Tissue-Derived Stem Cell Injections to Treat Cutaneous Radiation Syndrome: Preliminary Results. Health Phys. 111: 117-126.\n[13]\tRoszer T. (2015) Understanding the Mysterious M2 Macrophage through Activation Markers and Effector Mechanisms. Mediators of Inflammation Volume 2015 (2015), Article ID 816460, 16 pages.\n[14]\tSchiaffino S. et al., (2016) Regulatory T cells and skeletal muscle regeneration. FEBS J. Aug 1. doi: 10.1111/febs.13827.\n[15]\tTidball J.G. and Villalta S.A., (2010) Regulatory interactions between muscle and the immune system during muscle regeneration. Am J Physiol Regul Integr Comp Physiol. 298: 1173–1187.\n[16]\tTidball J.G et al., (2014) Shared signaling systems in myeloid cell-mediated muscle regeneration. Development. 141: 1184–1196.\n[17]\tVedeswari C.P. et al., (2009) In vivo autofluorescence characteristics of pre- and post-treated oral submucous fibrosis: A pilot study Indian J Dent Res. 20: 261-267.\n[18]\tVillalta S.A. et al., (2009) Shifts in macrophage phenotypes and macrophage competition for arginine metabolism affect the severity of muscle pathology in muscular dystrophy. Hum Mol Genet. 18: 482–496."]}

Background We raise the hypothesis that a STOP and GO strategy with induction by double immunotherapy Nivolumab + Ipilimumab combination during 6 months, followed by observation in patients with disease control (DC) at 6 months, would not be inferior to immunotherapy combination continuation until progression or unacceptable toxicity, in terms of progression-free survival, allowing lower toxicities cumulative rates, better quality of life and lower costs. Such strategy should not penalize overall survival, provided resuming immunotherapy at disease progression before second-line platinum-based chemotherapy. Trial design This is an open-label, randomized, phase III study in adult (≥18 years) patients, with stage IV non-small cell lung cancer, PD-L1 positive tumors, previously untreated for advanced disease. Subjects will first be locally assessed for PD-L1 expression, using 1% cut-off. Patients with enough tumor samples for central PD-L1 expression assessment, will be given first-line Nivolumab+Ipilumumab combination as followed: Nivolumab administered IV over 30 minutes at 3 mg/kg every 2 weeks combined with Ipilimumab administered IV over 30 minutes at 1 mg/kg every 6 weeks. Only patients with DC (objective response or stable disease), confirmed at 6 months, after a 1rst tumor evaluation at 3 months or beyond in case of pseudo-progression needing tumor reassessment, and without drug-related toxicity commanding treatment discontinuation will be randomized 1:1 either to continuation of Nivolumab+Ipilumumab combination until disease progression or unacceptable toxicity, or to clinical and radiological observation from week 24. Subjects receiving Nivolumab+Ipilimumab beyond investigator assessed progression must also continue tumor assessments until treatment discontinuation. Enrollment will end after approximately 868 subjects have been randomized (25/months). The primary endpoint of the study is Progression-Free Survival. Clinical trial identification NCT03469960. Legal entity responsible for the study IFCT (French Cooperative Thoracic Intergroup). Funding Bristol-Myers Squibb. Disclosure All authors have declared no conflicts of interest.

Background: Triple-negative (TN) and HER2-positive (HER2+) breast cancers have usually a worse prognosis than the luminal subtypes despite an initial chemosensitivity. The aim of this single-center study was to compare pathologic complete response (pCR) rates, disease-free (DFS) and overall (OS) survivals rates after neoadjuvant therapy according to both HER2 and hormonal status. Patients and Methods: Between 1978 and 2008, 461 patients were treated with neoadjuvant therapy at Georges-François Leclerc Cancer Center. Patients were classified in 3 groups: TN (defined by both estrogen/progesterone receptor negative and HER2 negative), HER2+ (3+ in immunohistochemistry or 2+ with amplification in fluorescence in situ hybridization) and HR+ (estrogen and/or progesterone receptor positive without HER2 overexpression or amplification). Median follow-up lasted 7.1 years [range: 0.49-29.8]. Number of events was 213 for DFS calculation and number of deaths was 150 for OS calculation. Response rates were compared using Chi2-tests. Survivals were calculated according to Kaplan-Meier and compared using log-rank tests. Univariate and multivariate Cox proportional hazards models were performed. The multivariate models were internally validated using bootstrapping (400 replications). Results: 86 of 461 were TN (19%), 125 were HER2+ (27%) and 250 were HR+ (54%). Patients with TN and HER2+ breast cancer were younger (p=0.032), had more inflammatory cancer (p=0.033) and aggressive tumors (SBR 3, P Median DFS was 4.4years for TN, 7.8y for HER2+ and 9y for HR+ (p=0.003, logrank test). In HER2+ patients, neoadjuvant trastuzumab was associated with a higher DFS (8.65 vs. 3.24y, p=0.002). Patients who achieved a pCR had a higher DFS (p=0.015) than those with only partial pathologic response (median=6.9y vs. 12.7y). In multivariate analysis, pCR remained significant (HR (bootstrapping) = 0.5 [IC95%, 0.28-0.91], p=0.023). Median OS was 6.4y for TN, 15.1y for HER2+ and 13.1y for HR+ (P50years (HR (bootstrapping)=1.79 [IC95%, 1.23-2.60], p=0.002), in TN subgroup (HR=2.46 [IC95%, 1.5-4.03], p=0.001) and when pCR was not achieved (HR=0.28, [IC95%, 0.12-0.66], p=0.003). Conclusion: After neoadjuvant therapy, TN breast cancers have a worse prognosis despite their initial chemosensitivity with a high pCR rate. HER2+ have a lower DFS than HR+/HER2- breast cancers but a better OS, mainly due to anti-HER2 targeted therapies. Pathologic complete response is a strong independent prognostic factor after neoadjuvant therapy for breast cancer. Citation Information: Cancer Res 2010;70(24 Suppl):Abstract nr P1-11-02.

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HER2-positive breast cancer accounts for 20 to 25% of breast cancers. The surexpression of this tyrosine-kinase receptor is often associated with a poor prognosis. However, the management and the outcome of these patients have changed these last ten years with trastuzumab. Despite the encouraging results obtained with this humanized monoclonal antibody directed against the HER2-receptor, used alone or in association with chemotherapy in metastatic patients, progression under trastuzumab are usually observed and resistances to this treatment are described. Thus, many other monoclonal antibodies and tyrosine-kinase inhibitors emerged. These therapeutics, used alone or in association with chemotherapy or trastuzumab have variable properties: anti-HER2 and anti-EGFR such as lapatinib, pertuzumab and neratinib; anti-EGFR such as erlotinib and gefitinib; antiangiogenesis (bevacizumab, pazopanib); anti-mTOR pathway (temsirolimus, everolimus) or inhibitor of HSP90 (tanespimycine). In this paper, we present an overview on validated targeted therapies and those which are currently under investigation and seem promising in first line or after progression under trastuzumab. Data regarding cardiotoxicity and the use of trastuzumab under particular clinical circumstances (brain metastases, pregnancy) are also reviewed.

Introduction We determined whether the implementation of a bundle of 10 recommendations leads to the reduction of mortality in ICU patients with severe sepsis or septic shock. Methods All patients with severe sepsis or septic shock during two consecutive phases: a 6-month quality control period (observational) and secondly a 6-month intervention period based on the implementation of a bundle of 10 recommendations adapted from the Surviving Sepsis Campaign guidelines (initial bacteriological samples and initiating antibiotics, measurement of arterial lactate, volume expansion ≥20 ml/kg, targeted mean arterial pressure ≥65 mmHg and the assessments of central venous pressure and ScvO2; glucose control, low doses of corticosteroids, a tidal volume ≤8 ml/kg in mechanically ventilated patients with ALI; adequate use of recombinant human activated protein C) were evaluated in 15 ICUs. The primary endpoint was the 28-day mortality rate and the secondary endpoint was the compliance with the recommendations of the care bundle. Measurement and results Four hundred and forty-five patients (230 and 215 in the observational and intervention periods, respectively) were included. In the two periods, the patients had similar characteristics. The 28-day mortality rate significantly decreased from 40% in the observational period to 27% in the intervention period (P = 0.02). According to each recommendation, compliance with the care bundle was achieved in 9 to 100% of patients. Conclusion The implementation of a care bundle adapted from the Surviving Sepsis Campaign guidelines decreases the 28-day mortality rate in patients with severe sepsis and/or septic shock.

Ces dernieres annees, des avancees importantes ont ete realisees dans le domaine de la recherche fondamentale et de transfert concernant les mecanismes impliques dans les processus d’acquisition d’un phenotype cancereux par une cellule normale du sein. Ces nouvelles acquisitions ont concerne la transduction du signal, le cycle cellulaire, l’apoptose, l’angiogenese, la migration et l’invasion cellulaire. Des nouvelles cibles therapeutiques potentielles ont ainsi ete identifiees et de nouvelles therapeutiques ciblees sont de ce fait developpees par des institutions academiques, des societes de biotechnologie et des compagnies pharmaceutiques. Certains de ces agents agissant sur des nouvelles cibles therapeutiques sont deja utilises en clinique, d’autres sont en evaluation. Nous nous interesserons essentiellement aux nouveaux agents (en dehors du trastuzumab, Herceptin®) intervenant au niveau de la transduction du signal et de l’angiogenese. L’hormonotherapie des cancers du sein est une therapeutique ciblee au niveau des recepteurs hormonaux œstrogeniques, nous evoquerons les echanges « cross talks » entre cette voie classique et la transduction du signal.

Introduction Nous avons souhaite connaitre les habitudes de prescription des medecins lors des derniers jours de vie d’un patient en soins palliatifs dans le service d’oncologie medicale du centre regional de lutte contre le cancer. Patientss et methodes Etude incluant tous les patients, en soins palliatifs terminaux, decedes en 2011 en oncologie medicale et y etant hospitalises depuis au moins 5 jours. Nous nous sommes focalises sur la prise en charge des principaux symptomes en se referant a l’ ABC of palliative care et le traitement des comorbidites. Resultats Parmi les 155 patients decedes en 2011, 90 ont pu etre inclus. Dans la prise en charge des symptomes, 93 % des patients ont un traitement antalgique ; dans la majorite des cas, c’est un palier 3. Dans la prise en charge des troubles digestifs, 12 % des patients ont un traitement antidiarrheique, 49 % un traitement laxatif, pres de la moitie un traitement antiulcereux et 44 % un traitement anti-emetique. Les prokinetiques sont les plus representes et 3 % des patients conservent un setron. En revanche, moins de la moitie des patients beneficient d’une prise en charge des mucites. Une hydratation IV est presente chez 69 % des patients et 32 % ont une nutrition avec ajout de complements vitaminiques dans un tiers des cas. On retrouve une prescription d’anxiolytique chez 78 % des patients et d’antidepresseurs chez 29 % d’entre eux. Dans le cadre de la prise en charge palliative, les morphiniques, les corticoides et le midazolam sont largement representes. Dans la prise en charge des comorbidites, nous avons notamment retrouve la prise en charge des troubles cardiaques et du diabete. Enfin, pres de 80 % des patients ont beneficie d’une surveillance biologique au cours de leur derniere semaine. Discussion La plupart des medicaments encore presents la derniere semaine avant le deces du patient rentrent dans la prise en charge palliative du patient afin de soulager ses douleurs, son inconfort et ses angoisses. Ainsi, les 3 specialites les plus prescrites sont les morphiniques (93 %), les corticoides (79 %) et les anxiolytiques (78 %). Nous pouvons nous interroger sur la pertinence de certaines prescriptions a ce stade de la maladie comme la prescription de setrons, de complements vitaminiques ou encore l’interet de bilans biologiques. Conclusion Ces resultats semblent concordants avec ce qui est decrit dans la litterature. Certains points restent a ameliorer comme une meilleure prise en charge de la mucite et un allegement de certains traitements.

Each of the 12 vertices of the adenovirus virion is made of penton, the complex of two oligomeric proteins: a pentameric penton base anchored in the capsid and an antenna-like trimeric fiber extending outwards. Adenovirus penton plays an essential role in the infection of host cells because it is indispensable for virus attachment and internalization. The initial interactions of penton with the primary and secondary receptors are well described. In contrast with that, the role of the penton components downstream of the initial cell contact is not known. This work shows for the first time that two adenovirus structural proteins, fiber and base, are able to interact intimately with different classes of cellular targets. In the case of penton base, a protein responsible for virus internalization, the partners include three ubiquitin-protein ligases that are involved in protein turnover, cell cycle control and endocytosis. Another base protein partner, BAG3, is involved in controlling Hsc70 chaperone activity. Virus attachment protein, fiber, interacts with many different partners, some of them involved in signal transduction and cell growth. Further work will illustrate the implications of these interactions for both the viral and cellular life cycles.

beta-Cyclodextrin (beta-CD) is a bile acid and sterol sequestrant produced by enzymatic modification of starch; this product has the potential to decrease plasma cholesterol. In contrast to the sequestrants having resin- or saponin-like properties, beta-CD is rapidly broken down by the large intestine microflora. beta-CD effects on cecal fermentations and lipid metabolism were thus investigated in rats adapted to semipurified diets containing 0%, 2.5%, or 5% beta-CD. In rats fed beta-CD diets, there was an enlargement of the cecum together with a dramatic increase in the cecal concentration of propionic acid (even with the 2.5% level, in moderately acidic pH conditions). Propionic acid produced in the cecum was readily absorbed and entirely taken up by the liver, whereas there was no significant acetic acid uptake. Dietary beta-CD was highly effective in enhancing bile acid entry into to the cecum: the cecal bile acids pool was 2.2 and 3.6-fold enlarged in rats fed the 2.5% and 5% beta-CD diets, respectively. The solubility percentage of bile acids decreased to approximately 25% in rats fed the beta-CD diets (v 51% in controls); the cecal concentration of soluble bile acids was thus relatively low in these animals. The fecal excretion of steroids was strongly enhanced by beta-CD, and bile acids excretion was practically proportional to the dietary beta-CD level. There was a net lipid-lowering effect of beta-CD, even at the 2.5% level. The effect was more pronounced on triglycerides than on cholesterol.(ABSTRACT TRUNCATED AT 250 WORDS)

Background: Triple negative breast cancer (TNBC) accounts for 15 to 20% of breast cancers. Despite initial chemosensitivity, patients with TNBC had a poor outcome with worse disease-free and overall survivals than others with non-triple-negative breast cancer. The aim of this single-center study was to describe clinical characteristics, pathologic complete response rate, disease-free survival and overall survival rates after neoadjuvant chemotherapy in TNBC.Methods: Forty six consecutive patients with TNBC were treated with neoadjuvant chemotherapy at Georges-François Leclerc Cancer Center. Median follow-up lasted 6.3 years [4.4-10.5y]. Descriptive statistics were performed in this population. Survival rates were calculated according to Kaplan-Meier.Results: Clinical characteristics of patients were the followings: median age was 46 years [24-80y]; 24% had a breast neoplastic hereditary. Initial characteristics of tumors were: 4 T1 (9%), 25 T2 (54%), 17 T3 (37%), 18 N0 (39%), 25 N1 (54%), 3 N2 (7%); 12 grades II (26%), 31 grades III (68%) and 3 (6%) unknown. All the tumors were invasive ductal carcinomas. After neoadjuvant chemotherapy, tumors were classified as pT0 (33%), pT1 (35%), pT2 (30%), pT3 (2%), pN0 (67%) and pN+ (33%). Forty patients (87%) were treated with anthracyclines-based neoadjuvant therapy, 4 (9%) with taxanes and 2 (4%) with another regimen. Pathologic complete response rate was 28.2% according to Chevallier's classification. Forty-five patients (98%) had adjuvant radiotherapy and 20 (43%) had adjuvant chemotherapy. Median disease-free survival was 9.7years [4.4-ND]. The disease-free survival rate was 82.4% [66.6%-91.2%] and 44.8% [23.7%-64%] at 2 and 10 years respectively. Median overall survival was 10.2years [6.4-ND]. The overall survival rate was 97.4% [86.2%-99.6%] and 53.7% [31.8%-71.5%] at 2 and 10 years respectively.Conclusion: The pathologic complete response rate is consistent with that reported in other studies involving neoadjuvant chemotherapy of TNBC and higher than that observed in the other subgroups of breast cancer. However, disease-free and overall survivals are lower than in non triple-negative breast cancers, thereby confirming the worse prognosis of TNBC Citation Information: Cancer Res 2009;69(24 Suppl):Abstract nr 1103.

Bisphenol A (BPA) and ethynylestradiol (EE2), two representative endocrine disrupting compounds (EDCs), were tested for their adsorbabilities onto two powdered activated carbons (PACs). The main aim of the study was to create a prediction tool for the determination of the EDCs adsorbabilities at low ng.L−1 level. Single solute solution adsorption isotherms at high concentrations, for prediction purposes, and low concentrations, for verification of the prediction, were performed for one EDC/PAC couple. Over the whole range of concentration, results showed that the Langmuir-Freundlich model better suits the adsorption phenomenon than the Freundlich or Langmuir model. Kinetics experiments were carried out on the same EDC/PAC couple. HSDM modelling of single solute adsorption kinetics at high concentration allowed determining the kinetic coefficients kf and Ds; both were shown to dominate the mass transfer mechanism. Competitive adsorption isotherms at high and low concentrations showed that downward extrapolation of low concentration adsorption capacities from solely high concentration information results in acceptable error compared to the total range isotherm. The IAST-EBC approach combined with the Langmuir-Freundlich single solute model, for the target compound, and the Langmuir model, for the EBC, appears as an acceptable global model.