Search

Abstract High-grade serous ovarian cancers (HGSOC) represent the most common subtype of ovarian malignancies. Due to the frequency of late-stage diagnosis and high rates of recurrence following standard of care treatments, novel therapies are needed to promote durable responses. We investigated the anti-tumor activity of CD3 T cell engaging bispecific antibodies (TCBs) directed against the PAX8 lineage-driven HGSOC tumor antigen LYPD1 and demonstrated that anti-LYPD1 TCBs induce T cell activation and promote in vivo tumor growth inhibition in LYPD1-expressing HGSOC. To selectively target LYPD1-expressing tumor cells with high expression while sparing cells with low expression, we coupled bivalent low-affinity anti-LYPD1 antigen-binding fragments (Fabs) with the anti-CD3 scFv. In contrast to the monovalent anti-LYPD1 high-affinity TCB (VHP354), the bivalent low-affinity anti-LYPD1 TCB (QZC131) demonstrated antigen density-dependent selectivity and showed tolerability in cynomolgus monkeys at the maximum dose tested of 3 mg/kg. Collectively, these data demonstrate that bivalent TCBs directed against LYPD1 have compelling efficacy and safety profiles to support its use as a treatment for high-grade serous ovarian cancers.

Circulating tumour cells contribute to metastatic spread. Here the authors find that beta-chain of haemoglobin is overexpressed in those cells and protects them from oxidative stress, prolonging their survival in circulation and thereby increasing the likelihood of metastasis formation.

Circulating tumor cells (CTCs) are shed from primary tumors into the bloodstream, mediating the hematogenous spread of cancer to distant organs. To define their composition, we compared genome-wide expression profiles of CTCs with matched primary tumors in a mouse model of pancreatic cancer, isolating individual CTCs using epitope-independent microfluidic capture, followed by single-cell RNA sequencing. CTCs clustered separately from primary tumors and tumor-derived cell lines, showing low-proliferative signatures, enrichment for the stem-cell-associated gene Aldh1a2, biphenotypic expression of epithelial and mesenchymal markers, and expression of Igfbp5, a gene transcript enriched at the epithelial-stromal interface. Mouse as well as human pancreatic CTCs exhibit a very high expression of stromal-derived extracellular matrix (ECM) proteins, including SPARC, whose knockdown in cancer cells suppresses cell migration and invasiveness. The aberrant expression by CTCs of stromal ECM genes points to their contribution of microenvironmental signals for the spread of cancer to distant organs.

La mise à jour de bases de données d'occupation du sol (BD OCS), comme la base OCS à grande échelle (OCS-GE) développée à l'IGN, est un enjeu important dans le contexte environnemental actuel et les politiques publiques associées. En effet, ces bases de données nouvellement créées doivent permettre le suivi d'indicateurs, et donc être en permanence d'actualité. D'autre part, les images satellites très haute résolution (Pléiades) permettent un suivi régulier du territoire. Bien que le sujet de la détection de changements ait déjà beaucoup été abordé dans la littérature, des améliorations doivent encore être apportées pour les rendre plus opérationnelles. Ainsi, nous proposons dans cet article, un certain nombre d'améliorations en terme de polyvalence et de passage à l'échelle d'une méthode de détection de changements existante (Gressin et al., 2013), afin de permettre le traitement de la BD d'OCS-GE de l'IGN à partir d'une image satellite monoscopique Pléiades. Enfin, différents résultats, dont la comparaison avec des méthodes de l'état de l'art et l'application à la BD OCS-GE, sont présentés dans ce papier.

PURPOSE: The objective was to check if 520 days in confinement (MARS 500), may affect the main peripheral arterial diameter and wall thickness and the main vein size. METHOD: Common carotid (CC) femoral artery (FA) portal vein (PV), jugular (JG), femoral vein (FV) and tibial vein were assessed during MARS 500 by echography, performed by the subjects. A hand free volumic echographic capture method and a delayed 3D reconstruction software developed by our lab were used for collecting and measuring the vascular parameters. RESULTS: During the MARS 500 experiment the subjects performed 6 sessions among which 80% of the echographic data were of sufficient quality to be processed. No significant change was found for the Common carotid, Jugular vein, femoral artery, femoral vein, portal vein, and tibial vein diameter. CC and FA IMT (intima media thickness) were found significantly increased (14% to 28% P

In this paper we introduce the numerical tools that have been developed in the context of the Graphem project, in order to automate or leverage several steps in the study of medieval writing samples. We first describe various kinds of features that have been extracted from the samples, and then present two graphical tools to compare writing samples according to the features that have been extracted.

TGF-β secreted by tumor stroma induces epithelial-to-mesenchymal transition (EMT) in cancer cells, a reversible phenotype linked to cancer progression and drug resistance. However, exposure to stromal signals may also lead to heritable changes in cancer cells, which are poorly understood. We show that epithelial cells failing to undergo proliferation arrest during TGF-β-induced EMT sustain mitotic abnormalities due to failed cytokinesis, resulting in aneuploidy. This genomic instability is associated with the suppression of multiple nuclear envelope proteins implicated in mitotic regulation and is phenocopied by modulating the expression of LaminB1. While TGF-β-induced mitotic defects in proliferating cells are reversible upon its withdrawal, the acquired genomic abnormalities persist, leading to increased tumorigenic phenotypes. In metastatic breast cancer patients, increased mesenchymal marker expression within single circulating tumor cells is correlated with genomic instability. These observations identify a mechanism whereby microenvironment-derived signals trigger heritable genetic changes within cancer cells, contributing to tumor evolution.