Generation of full-length circular RNA libraries for Oxford Nanopore long-read sequencing.

Circular RNA (circRNA) is a noncoding RNA class with important implications for gene expression regulation, mostly by interaction with other RNA species or RNA-binding proteins. While the commonly applied short-read Illumina RNA-sequencing techniques can be used to detect circRNAs, their full sequence is not revealed. However, the complete sequence information is needed to analyze potential interactions and thus the mechanism of action of circRNAs.

Tripartite split-GFP assay to identify selective intracellular nanobody that suppresses GTPase RHOA subfamily downstream signaling.

Strategies based on intracellular expression of artificial binding domains present several advantages over manipulating nucleic acid expression or the use of small molecule inhibitors. Intracellularly-functional nanobodies can be considered as promising macrodrugs to study key signaling pathways by interfering with protein-protein interactions. With the aim of studying the RAS-related small GTPase RHOA family, we previously isolated, from a synthetic phage display library, nanobodies selective towards the GTP-bound conformation of RHOA subfamily proteins that lack selectivity between the highly conserved RHOA-like and RAC subfamilies of GTPases.

A New Saharan Strain of Streptomyces sp. GSB-11 Produces Maculosin and N-acetyltyramine Active Against Multidrug-Resistant Pathogenic Bacteria.

Multi-resistant bacterial pathogens are a major public health problem for treating nosocomial infections owing to their high resistance to antibiotics. The objective of this research was to characterize the bioactive molecules secreted by a novel moderately halophilic actinobacterium strain, designated GSB-11, exhibiting a strong antagonistic activity against several multidrug-resistant pathogenic bacteria. This potential strain was identified by phenotypic, genotypic (16S rRNA), and phylogenetic analyses.

Circulating Exhausted PD-1CD39 Helper CD4 T Cells Are Tumor-Antigen-Specific and Predict Response to PD-1/PD-L1 Axis Blockade.

Tumor-infiltrating exhausted PD-1CD39 tumor-antigen (Ag)-specific CD4 T cells contribute to the response to immune checkpoint blockade (ICB), but their circulating counterparts, which could represent accessible biomarkers, have not been assessed. Here, we analyzed circulating PD-1CD39 CD4 T cells and show that this population was present at higher proportions in cancer patients than in healthy individuals and was enriched in activated HLA-DR and ICOS and proliferating KI67 cells, indicative of their involvement in ongoing immune responses. Among memory CD4 T cells, this population contained the lowest proportions of cells producing effector cytokines, suggesting they were exhausted.

Antibody-Based Approaches to Target Pancreatic Tumours.

Pancreatic cancer is an aggressive cancer with a dismal prognosis. This is due to the difficulty to detect the disease at an early and curable stage. In addition, only limited treatment options are available, and they are confronted by mechanisms of resistance.

The beginning of a new therapeutic era in acute myeloid leukemia.

In the field of AML, the early 2000s were shaped by the advent of novel molecular biology technologies including high-throughput sequencing that improved prognostic classification, response evaluation through the quantification of minimal residual disease, and the launch of research on targeted therapies. Our knowledge of leukemogenesis, AML genetic diversity, gene-gene interactions, clonal evolution, and treatment response assessment has also greatly improved. New classifications based on chromosomal abnormalities and gene mutations are now integrated on a routine basis.

[Resistance to BRAF inhibitors: A lesson from clinical observations].

The MAPK/ERK pathway is an essential intracellular signaling pathway. Its deregulation is involved in tumor transformation and progression. The discovery of activating mutations of BRAF in various cancers has opened new therapeutic avenues with BRAF protein kinase inhibitors.

Slow-Fast Model and Therapy Optimization for Oncolytic Treatment of Tumors.

The present work studies models of oncolytic virotherapy without space variable in which virus replication occurs at a faster time scale than tumor growth. We address the questions of the modeling of virus injection in this slow-fast system and of the optimal timing for different treatment strategies. To this aim, we first derive the asymptotic of a three-species slow-fast model and obtain a two-species dynamical system, where the variables are tumor cells and infected tumor cells.

Hexokinase 3 enhances myeloid cell survival via non-glycolytic functions.

The family of hexokinases (HKs) catalyzes the first step of glycolysis, the ATP-dependent phosphorylation of glucose to glucose-6-phosphate. While HK1 and HK2 are ubiquitously expressed, the less well-studied HK3 is primarily expressed in hematopoietic cells and tissues and is highly upregulated during terminal differentiation of some acute myeloid leukemia (AML) cell line models. Here we show that expression of HK3 is predominantly originating from myeloid cells and that the upregulation of this glycolytic enzyme is not restricted to differentiation of leukemic cells but also occurs during ex vivo myeloid differentiation of healthy CD34 hematopoietic stem and progenitor cells.

Monoallelic Deletion Reduces the Requirement for NOTCH1 Hyperactivation in T-Cell Acute Lymphoblastic Leukemia.

Early T-cell development is precisely controlled by E proteins, that indistinguishably include HEB/TCF12 and E2A/TCF3 transcription factors, together with NOTCH1 and pre-T cell receptor (TCR) signalling. Importantly, perturbations of early T-cell regulatory networks are implicated in leukemogenesis. NOTCH1 gain of function mutations invariably lead to T-cell acute lymphoblastic leukemia (T-ALL), whereas inhibition of E proteins accelerates leukemogenesis.

Field output correction factors and electron fluence perturbation of the microSilicon and microSilicon X detectors.

The aim of this study was to determine field output correction factorskQclin,Qreffclin,frefand electron fluence perturbation for new PTW unshielded microSilicon and shielded microSilicon X detectors.kQclin,Qreffclin,freffactors were calculated for 6 and 10 MV with and without flattening filter beams delivered by a TrueBeam STx. Correction factors were determined for field sizes ranging from 0.

Adipocyte Extracellular Vesicles Decrease p16 in Melanoma: An Additional Link between Obesity and Cancer.

Obesity is a recognized factor for increased risk and poor prognosis of many cancers, including melanoma. In this study, using genetically engineered mouse models of melanoma (Nras transgenic expression, associated or not with Cdkn2a heterozygous deletion), we show that obesity increases melanoma initiation and progression by supporting tumor growth and metastasis, thereby reducing survival. This effect is associated with a decrease in p16 expression in tumors.

Improving the Quality of EDTA-treated Blood Specimens from Mice.

Nonterminal blood sampling in laboratory mice is a very common procedure. With the goal of improving animal welfare, different sampling sites and methods have been compared but have not achieved a consensus. Moreover, most of these studies overlooked the quality of blood specimens collected.

IL-10 Rescues CLL Survival through Repolarization of Inflammatory Nurse-like Cells.

Tumor-associated macrophages (TAMs) in chronic lymphocytic leukemia (CLL) are also called nurse-like cells (NLC), and confer survival signals through the release of soluble factors and cellular contacts. While in most patient samples the presence of NLC in co-cultures guarantees high viability of leukemic cells in vitro, in some cases this protective effect is absent. These macrophages are characterized by an "M1-like phenotype".

Radiotherapy of lymphomas.

Radiotherapy for Hodgkin lymphomas has evolved a lot over time, but still plays an important role, almost always in addition to chemotherapy, for the management of the early stages. The major objective is to preserve the quality of life of patients who will be cured from this disease in the vast majority of cases. Also, the personalization of the indications for the purpose of de-escalating toxicity is very refined and is essentially based on the pre- and pertherapeutic assessment by FDG-PET.

Respiratory motion management for external radiotherapy treatment.

We present the update of the recommendations of the French society of oncological radiotherapy on respiratory motion management for external radiotherapy treatment. Since twenty years and the report 62 of ICRU, motion management during the course of radiotherapy treatment has become an increasingly significant concern, particularly with the development of hypofractionated treatments under stereotactic conditions, using reduced safety margins. This article related orders of motion amplitudes for different organs as well as the definition of the margins in radiotherapy.

Clinically Relevant Oxygraphic Assay to Assess Mitochondrial Energy Metabolism in Acute Myeloid Leukemia Patients.

Resistant acute myeloid leukemia (AML) exhibits mitochondrial energy metabolism changes compared to newly diagnosed AML. This phenotype is often observed by evaluating the mitochondrial oxygen consumption of blasts, but most of the oximetry protocols were established from leukemia cell lines without validation on primary leukemia cells. Moreover, the cultures and storage conditions of blasts freshly extracted from patient blood or bone marrow cause stress, which must be evaluated before determining oxidative phosphorylation (OXPHOS).

Antagonistic Roles of the Tumor Suppressor miR-210-3p and Oncomucin MUC4 Forming a Negative Feedback Loop in Pancreatic Adenocarcinoma.

Background: Pancreatic adenocarcinoma (PDAC) is a deadly cancer with an extremely poor prognosis. MUC4 membrane-bound mucin is neoexpressed in early pancreatic neoplastic lesions and is associated with PDAC progression and chemoresistance. In cancers, microRNAs (miRNAs, small noncoding RNAs) are crucial regulators of carcinogenesis, chemotherapy response and even metastatic processes.

Pharmacogenomics in solid cancers and hematologic malignancies: Improving personalized drug prescription.

The discovery of molecular alterations involved in oncogenesis is evolving rapidly and has led to the development of new innovative targeted therapies in oncology. High-throughput sequencing techniques help to identify genomic targets and to provide predictive molecular biomarkers of response to guide alternative therapeutic strategies. Besides the emergence of these theranostic markers for the new targeted treatments, pharmacogenetic markers (corresponding to genetic variants existing in the constitutional DNA, i.