Organisation et dynamique des microtubules (rôles de la tubuline-GTP et de CLIP-170)

Les microtubules sont des polymères de tubuline, très dynamiques, essentiels à de nombreuses fonctions cellulaires telles que la division, le trafic intracellulaire et la migration. Ils alternent entre des phases de croissance et décroissance, séparées par des événements de catastrophe et de sauvetage. L équipe a montré que la tubuline-GTP est présente sous forme d îlots le long des microtubules. Nous avons proposé un nouveau modèle d instabilité dynamique selon lequel les îlots de tubuline-GTP, exposés lors de la dépolymérisation des microtubules, favoriseraient les sauvetages. Durant ma thèse, je me suis intéressée à la régulation et aux rôles de ces îlots de tubuline-GTP. J ai montré que les intersections entre les microtubules in vivo présentent une accumulation de la tubuline-GTP. Par des expériences de reconstitution menées in vitro j'ai montré que l accumulation de tubuline-GTP aux intersections est intrinsèque et indépendante de protéines associées aux microtubules. Ces intersections montrent un fort biais dans la localisation des événements de sauvetages in vivo et présentent aussi une rétention du facteur de sauvetage CLIP-170. Cette localisation et ce rôle de CLIP-170 aux croisements semblent être indépendants des protéines EB. Ces résultats confirment le rôle de la tubuline-GTP dans la régulation de la dynamique des microtubules et suggèrent que l organisation du réseau de microtubules dans la cellule participe directement à la régulation de sa propre dynamiqueMicrotubules (MTs) are tubulin polymers that are essential in many cellular functions such as division, intracellular trafficking and cell migration. They undergo dynamic instability and alternate between phases of growth and shrinkage separated by catastrophe and rescue events. We showed in a previous study that GTP-tubulin is present not only at the plus end of growing MTs, but also in discrete locations forming GTP-islands along the MT lattice. We proposed a new model for dynamic instability in which GTP-tubulin islands, exposed during depolymerization, would promote rescue events. During my PhD, I studied the regulation and roles of GTP-tubulin islands. I showed that MT intersections present a strong positive bias towards the occurrence of GTP-tubulin islands. Experiments carried out in vitro indicated that the accumulation of GTP-tubulin at intersections is independent of MT-associated proteins. In cells, we observed that MT intersections strongly correlate with hotspots for microtubule rescues and we found that they are also frequent sites of retention of the rescue factor CLIP-170. This localization and role of CLIP-170 seem to be independent from EB proteins. These results confirm the role of GTP-tubulin in the regulation of MT dynamics and suggest that the organization of the whole MT network contribute to the regulation of its dynamicsPARIS-BIUSJ-Biologie recherche (751052107) / SudocSudocFranceF

‘Bad news consultations’ with oncology nurses: Impact on perceived stress and patient experience

International audiencePurpose: ‘Bad News Consultations’ (BNC), conducted by nurses who are specialists in cancer, have been institutionally implemented in all French anti-cancer centres, to support the patient facing announcement-related stress. This study aimed to 1/describe the impact of the BNC on the patient's perceived stress and 2/determine the patient's benefits from the BNC.Method: This monocentric study, cross-sectional evaluation, used a mixed method, both quantitative and qualitative. During 8 months, 336 eligible participants who underwent a BNC were recruited by nurses. Perceived stress was self-assessed with a validated Visual Analogic Scale (VAS), at the beginning and at the end of the BNC. Stress resilience was self-assessed once using the CD-RISC2. Qualitative experiences were explored after the BNC, using a 25-item questionnaire. Multivariate analyses were conducted on perceived stress measures (on the VAS) to test mixed-effects models, including initial predispositions (e.g., stress resilience) and organisational constraints (e.g, interval between the medical consultation and the BNC).Results: Analyses on the perceived stress measures revealed a significant and negative effect of Time (B = −1.91; p < .001), Gender (B = 0.72; p = .03), and Resilience score (B = −0.43; p < .001), without any significant effect of the other incorporated random effects (i.e., Type of cancer/treatment) nor fixed effects (i.e., Age, Organisational constraints). Patients mostly reported having received necessary information, having their addressed emotions with empathetic responses and respect, perceived benefits in the healthcare pathway, and heard of some supportive cares.Conclusion: Perceived stress was reduced after BNCs. According to the patients, the BNCs allowed a better patient-centered communication and a better care pathway

Feasibility and tolerability of self-insertion of a transnasal tube for esophagogastroduodenoscopy: a pilot study

International audienc

Microwave Ablation of Liver, Kidney and Lung Lesions: One-Month Response and Manufacturer&rsquo;s Charts&rsquo; Reliability in Clinical Practice

Microwave ablation systems allow for performing tumoral destruction in oncology. The objective of this study was to assess the early response and reliability of the microwave ablation zone size at one month for liver, kidney and lung lesions, as compared to the manufacturer&rsquo;s charts. Patients who underwent microwave ablation with the EmprintTM ablation system for liver, kidney and lung lesions between June 2016 and June 2018 were retrospectively reviewed. Local response and ablation zone size (major, L, and minor, l, axes) were evaluated on the one-month follow-up imaging. Results were compared to the manufacturers&rsquo; charts using the Bland&ndash;Altman analysis. Fifty-five patients (mean age 68 &plusmn; 11 years; 95 lesions) were included. The one-month complete response was 94%. Liver ablations showed a good agreement with subtle, smaller ablation zones (L: &minus;2 &plusmn; 5.7 mm; l: &minus;5.2 &plusmn; 5.6 mm). Kidney ablations showed a moderate agreement with larger ablations for L (L: 8.69 &plusmn; 7.94 mm; l: 0.36 &plusmn; 4.77 mm). Lung ablations showed a moderate agreement, with smaller ablations for l (L: &minus;5.45 &plusmn; 4.5 mm; l: &minus;9.32 &plusmn; 4.72 mm). With 94% of early complete responses, the system showed reliable ablations for liver lesions, but larger ablations for kidney lesions, and smaller for lung lesions

Localized Mechanical Stress Promotes Microtubule Rescue

International audienc

Feasibility and Safety of Single-Probe Cryoablation with Liquid Nitrogen: An Initial Experience in 24 Various Tumor Lesions

Background: Percutaneous cryoablation with liquid nitrogen is a new technique being used in the treatment of some malignant tumors. Our objective was to assess its feasibility in the ablation of tumor lesions of various sizes and locations. Methods: This retrospective, monocentric study included all consecutive patients who underwent percutaneous cryoablation with liquid nitrogen between December 2019 and March 2021. Cryoablation was performed using 10G or 13G cryoprobes. The ablation volume was measured on post-treatment CT or MRI. Results: 22 patients (24 lesions) were included, 16 of whom were men (73%), while median age was 66 years. The lesions were located in the bone (42%), kidney (29%), soft tissue (17%), lung (8%), or liver (4%). It was feasible in all tumor locations and produced median ablation zones 25 mm in width and 35 mm in length, with a 23 min median freezing time. Freezing duration was correlated with the ice volume (p Spearman = 0.02), but not with the ablation volume (p = 0.11). The average difference between the ablation zone and ice ball sizes were &minus;6.4 mm in width and &minus;7.7 mm in length. Both ice and ablation volumes were larger when using the 10G probe as compared to when the 13G was used. No complications were reported. Discussion: We showed that this technique was safe and feasible in all organs tested. The freezing duration was correlated with the ice ball size, but not with the ablation zone

Preoperative intraperitoneal oxaliplatin for unresectable peritoneal carcinomatosis of colorectal origin: a pilot study

International audienceBackground:Peritoneal carcinomatosis in colorectal cancer is an advanced stage of the disease where improved survival can be attained whenever the resection associated with hyperthermic intreperitoneal chemotherapy is possible. In unresectable cases, systemic chemotherapy is administered to obtain conversion to resectability but results have not yet been clearly evaluated. Local chemotherapy in this setting has been proven useful in several similar situations. The aim of the present pilot study was to evaluate the feasibility of pre-operative intraperitoneal chemotherapy with oxaliplatin in these patients.Methods:Six patients with unresectable peritoneal disease of colorectal origin were included in the study. An intraperitoneal implantable chamber catheter was inserted during the laparotomy that evaluated the extent of the peritoneal disease (peritoneal carcinomatosis index 25 to 39). Patients then underwent intraperitoneal chemotherapy with oxaliplatin 85 mg/m2 in combination with systemic chemotherapy (FOLFIRI or simplified LV5FU) and a targeted therapy every 2 weeks.Results:Two catheter perfusion incidents were reported due to the abdominal wall thickness. Two patients completed the four intraperitoneal (IP) chemotherapy cycles without major toxicity. One patient developed grade 3 or 4 diarrhea requiring a short intensive care unit (ICU) stay, though it is not clear whether the event was induced by intravenous irinotecan, IP oxaliplatin or the combination of both. Grade 3 fatigue and abdominal pain were also recorded. For one patient with aggressive disease, best supportive care was initiated after the first course of chemotherapy.Conclusions:Our study is the first to assess intraperitoneal oxaliplatin-based chemotherapy in the preoperative setting for patients with unresectable peritoneal metastases. The tolerance was acceptable for 85 mg/m2 IP oxaliplatin combined with systemic therapy in these patients. Our results justify carrying on with a phase I/II trial to determine the recommended dose of oxaliplatin in this clinical context and its efficacy

Systematic review and meta-analysis on the impact of lung cancer screening by low-dose computed tomography

International audienceLung cancer (LC) has the highest cancer mortality worldwide with poor prognosis. Screening with low-dose computed tomography (LDCT) in populations highly exposed to tobacco has been proposed to improve LC prognosis. Our objective was to perform a systematic review and meta-analysis to evaluate the efficacy of screening by LDCT compared with any other intervention in populations who reported tobacco consumption for more than 15 years on LC and overall mortality.Methods: We searched randomised controlled trials (RCTs) studying screening by LDCT compared with any other intervention in a population who reported an average smoking history greater than 15 pack-years from inception until the 19th February 2018 using Medline and Cochrane Library databases. Publication selection and data extraction were made independently by two double-blind reviewers.Results: Seven RCTs were included in the meta-analysis which corresponds to 84,558 participants. A significant relative reduction of LC-specific mortality of 17% (risk ratio [RR] = 0.83, 95% confidence interval [CI]: 0.76-0.91) and a relative reduction of overall mortality of 4% (RR = 0.96, 95% CI: 0.92-1.00) was observed in the screening group compared with the control group.Conclusion: In populations highly exposed to tobacco, screening by LDCT reduces lung cancer mortality

Importance of Patient Education for At-home Yoga Practice in Women With Hormonal Therapy-induced Pain During Adjuvant Breast Cancer Treatment: A Feasibility Study

International audienceBackground Osteo-articular pain (OAP) is experienced by approximately 50% of women under hormonal therapy (HT) for breast cancer (BC), which increases the risk for therapy discontinuation. This study was aimed to assess benefits of yoga practice combined with patient education (PE) for at-home practice by evaluating feasibility among BC patients under HT and measuring OAP, flexibility and satisfaction.Methods Feasibility was evaluated by patient adherence as accomplishment of at least 4 out of 6 supervised yoga-PE sessions along with 70% or more at-home yoga sessions. Intervention (12 weeks) included two 6-weeks periods: P1 comprising one 90-minutes supervised yoga-PE session/week and 15-minutes daily at-home yoga and P2, daily autonomous at-home yoga sessions. Evaluations (at inclusion and by the end of each period) consisted in assessment of OAP on Visual Analog Scale (VAS), forward flexibility (cm) and patient satisfaction on Likert (0-10 points) scale.Results Between September 2018 and May 2019 we included 24 patients of median 53 years (range 36-72). Feasibility was validated by 83% successful adherence rate. Pain was significantly reduced from median VAS of 6 [range 4-10] to 4 [range 0-7] at the end of both P1 and P2 ( p < 0.01), albeit with no difference between P1 and P2. Forward flexibility improved by a median gain of 8 cm (end of P2) and median satisfaction score of 10/10 [range 8-10].Conclusion Combined physiotherapy-yoga-PE intervention is a feasible strategy to increase at-home yoga practice with potential benefit on pain, flexibility, and satisfaction, thus prompting further evaluations in larger randomized multicenter trials.ClinicalTrials.gov NCT0400175