Cet article revient sur deux projets militants menés par des étudiant-e-s d’une grande école, en lien avec sa référente égalité femmes-hommes. Il analyse les mécanismes qui ont conduit à l’aliénation ...des militant-e-s, leurs luttes étant accaparées par l’École. Cinq mécanismes sont identifiés : l’acquiescement sans suite, la confiscation des temporalités, l’évincement tacite des espaces de discussion, la familiarité avec l’administration et la peur du résultat. Il propose alors des stratégies mobilisables dans le cadre du militantisme étudiant. Ce faisant, ce retour d’expérience révèle comment un établissement ayant opté pour une communication marketing basée sur la mise en avant d’un discours féministe peut être enclin à prendre des décisions néfastes pour le militantisme féministe et LGBTQ+ étudiant dans le but de rester attractif auprès des investisseurs. En outre, il interroge l’effectivité des missions égalité femmes-hommes, dispositifs rendus obligatoires dans l’enseignement supérieur depuis 2013, lorsque celles-ci sont « managérialisées » afin de servir les intérêts de l’École.
This article draws upon two struggles led by student activists in which the gender equality advisor acted as an intermediary. It analyses the mechanisms through which the activists became alienated ...within their own struggles, as the latter were monopolised by their higher education institution. It highlights five mechanisms: positive answers without further action, confiscation of time management, exclusion from the discussion groups, familiarity with the school managers and fear of the result. It suggests several strategies for future student mobilisations. As gender equality missions are mandatory in French universities since 2013, this article questions the effectiveness of these missions once they are “manageralised” in order to serve the school interests, especially when the institution’s priority is the attraction and satisfaction of investors. This case study shows the negative impact of a communication strategy based on a feminist discourse on feminist and LGBTQ+ student activism.
Meningiomas are the most frequent primary intracranial tumors. Patient outcome varies widely from benign to highly aggressive, ultimately fatal courses. Reliable identification of risk of progression ...for individual patients is of pivotal importance. However, only biomarkers for highly aggressive tumors are established (
and
), whereas no molecularly based stratification exists for the broad spectrum of patients with low- and intermediate-risk meningioma.
DNA methylation data and copy-number information were generated for 3,031 meningiomas (2,868 patients), and mutation data for 858 samples. DNA methylation subgroups, copy-number variations (CNVs), mutations, and WHO grading were analyzed. Prediction power for outcome was assessed in a retrospective cohort of 514 patients, validated on a retrospective cohort of 184, and on a prospective cohort of 287 multicenter cases.
Both CNV- and methylation family-based subgrouping independently resulted in increased prediction accuracy of risk of recurrence compared with the WHO classification (c-indexes WHO 2016, CNV, and methylation family 0.699, 0.706, and 0.721, respectively). Merging all risk stratification approaches into an integrated molecular-morphologic score resulted in further substantial increase in accuracy (c-index 0.744). This integrated score consistently provided superior accuracy in all three cohorts, significantly outperforming WHO grading (c-index difference
= .005). Besides the overall stratification advantage, the integrated score separates more precisely for risk of progression at the diagnostically challenging interface of WHO grade 1 and grade 2 tumors (hazard ratio 4.34 2.48-7.57 and 3.34 1.28-8.72 retrospective and prospective validation cohorts, respectively).
Merging these layers of histologic and molecular data into an integrated, three-tiered score significantly improves the precision in meningioma stratification. Implementation into diagnostic routine informs clinical decision making for patients with meningioma on the basis of robust outcome prediction.
Pancreatic neuroendocrine tumors (NETs) are rare neoplasms for which surgery has almost the only potential for cure. When surgery is not possible because of tumor size and vascular involvement, ...neoadjuvant treatment with (177)Lu-DOTA(0),Tyr(3)octreotate ((177)Lu-octreotate) may be an option.
We studied 29 Dutch patients with a pathology-proven nonfunctioning pancreatic NET treated with (177)Lu-octreotate. All patients had a borderline or unresectable pancreatic tumor (group 1) or oligometastatic disease (defined as ≤3 liver metastases) (group 2). Progression-free survival (PFS) was analyzed using the Kaplan-Meier method and Cox proportional hazards modeling.
After the treatment with (177)Lu-octreotate, successful surgery was performed in 9 of 29 patients (31%). Six patients had a Whipple procedure, 2 patients had a pylorus-preserving pancreaticoduodenectomy, and 1 patient had a distal pancreatectomy and splenectomy. The median PFS was 69 mo for patients with successful surgery and 49 mo for the other patients. For comparison, the median PFS in 90 other patients with a nonfunctioning pancreatic NET with more than 3 liver metastases or other metastases was 25 mo.
Neoadjuvant treatment with (177)Lu-octreotate is a valuable option for patients with initially unresectable pancreatic NETs.
The peptide PVGLIG, which is known to be selectively cleaved by the tumor-associated enzyme matrix metalloproteinase-2 (MMP-2), was conjugated to α-alkene poly(trimethylene carbonate) (PTMC) blocks ...of varying sizes via UV-initiated thiol-ene “click” chemistry. The PTMC precursor was synthesized by metal-free ring-opening polymerization using allyl alcohol as an initiator and an N-heterocyclic carbene as an organic catalyst. The unprecedented PVGLIG-b-PTMC hybrids were self-assembled in aqueous solution and various submicrometer-sized morphologies obtained by a nanoprecipitation process. Characterization of particle morphology was carried out by multiangle dynamic light scattering (DLS) and static light scattering (SLS) evidencing spherical nanoparticles with different morphologies and narrow size distributions. Microstructure details were also observed on transmission electron micrographs and were in good agreement with light scattering measurements showing the assembly of core–shell, large compound micelles, and vesicle morphologies, the particle morphology varying with the hydrophilic weight fractions (f) of the hybrids. These nanostructures displayed selective degradation in the presence of the cancer-associated enzyme MMP-2, as probed by the morphological change both by TEM and DLS. All these results demonstrated that PVGLIG-b-PTMC hybrids were suitable to target the tumor microenvironment.
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IJS, KILJ, NUK, PNG, UL, UM
AMG 110, a bispecific T cell engager (BiTE) antibody construct, induces T cell-mediated cancer cell death by cross-linking epithelial cell adhesion molecule (EpCAM) on tumor cells with a cluster of ...differentiation 3 ε (CD3ε) on T cells. We labeled AMG 110 with (89)Zr or near-infrared fluorescent dye (IRDye) 800CW to study its tumor targeting and tissue distribution.
Biodistribution and tumor uptake of (89)Zr-AMG 110 was studied up to 6 d after intravenous administration to nude BALB/c mice bearing high EpCAM-expressing HT-29 colorectal cancer xenografts. Tumor uptake of (89)Zr-AMG 110 was compared with uptake in head and neck squamous cell cancer FaDu (intermediate EpCAM) and promyelocytic leukemia HL60 (EpCAM-negative) xenografts. Intratumoral distribution in HT-29 tumors was studied using 800CW-AMG 110.
Tumor uptake of (89)Zr-AMG 110 can be clearly visualized using small-animal PET imaging up to 72 h after injection. The highest tumor uptake of (89)Zr-AMG 110 at the 40-μg dose level was observed at 6 and 24 h (respectively, 5.35 ± 0.22 and 5.30 ± 0.20 percentage injected dose per gram; n = 3 and 4). Tumor uptake of (89)Zr-AMG 110 was EpCAM-specific and correlated with EpCAM expression. 800CW-AMG 110 accumulated at the tumor cell surface in viable EpCAM-expressing tumor tissue.
PET and fluorescent imaging provided real-time information about AMG 110 distribution and tumor uptake in vivo. Our data support using (89)Zr and IRDye 800CW to evaluate tumor and tissue uptake kinetics of bispecific T cell engager antibody constructs in preclinical and clinical settings.
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•PTMC50-b-PVGLIG-b-PGA15 triblock copolymer was synthesized.•Polymersomes were formed by self-assembly.•Specific degradation occurred in the presence of MMP2 enzyme.•Drug release was ...enhanced in the presence of MMP2 enzyme.
The synthetic semi-crystalline polymer poly(trimethylene carbonate) PTMC50 was linked to the synthetic poly(amino acid) poly(glutamic acid) (PGA15) using the peptide PVGLIG, known to be selectively cleaved by the tumor-associated enzyme matrix metalloproteinase 2 (MMP-2), by a combination of thiol-ene coupling and ring-opening polymerization. Stable, monodisperse, sub-micron sized polymersomes were subsequently obtained by self-assembly and characterized by dynamic and static light scattering (DLS and SLS) and transmission electron microscopy (TEM). These vesicles showed selective degradation in the presence of MMP-2 as probed by DLS. The model drug imipramine hydrochloride was loaded at 35% encapsulation efficiency by co-precipitation and displayed controlled drug-release behavior. Drug release rates showed several fold increases when exposed to pH, temperature and most significantly, to the tumor-associated enzyme MMP-2. Such structures, bearing precise location of the cleavable peptide sequence, may hold promise as future specific and controlled drug-delivery systems.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK
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