Exploring the Transport Path of Oceanic Microplastics in the Atmosphere.

Microplastics (MP) have been recognized as an emerging atmospheric pollutant, yet uncertainties persist in their emissions and concentrations. With a bottom-up approach, we estimate 6-hourly MP fluxes at the ocean-atmosphere interface, using as an input the monthly ocean surface MP concentrations simulated by the global oceanic model (NEMO/PISCES-PLASTIC, Nucleus for European Modeling of the Ocean, Pelagic Interaction Scheme for Carbon and Ecosystem Studies), a size distribution estimate for the MP in the micrometer range, and a sea salt emission scheme. The atmospheric dispersion is then simulated with the Lagrangian model FLEXPART.

Influence of waves on the three-dimensional distribution of plastic in the ocean.

The world's oceans are facing plastic pollution, 80 % of which of terrestrial origin flowing from the mismanaged waste of coastal populations and from river discharge. To study the fate of this pollution, the three-dimensional trajectories of neutral plastic particles continuously released for 24 years according to realistic source scenarios are computed using currents from a global ocean-wave coupled model at 14 resolution and from a reference ocean-only model. These Lagrangian simulations show that neutral particles accumulate at the surface in the subtropical convergence zones from where they penetrate to about 250 m depth and strongly disperse over 40 of latitude.

Biogeochemical feedbacks associated with the response of micronutrient recycling by zooplankton to climate change.

Recycling by zooplankton has emerged as an important process driving the cycling of essential micronutrients in the upper ocean. Resupply of nutrients by upper ocean recycling is itself controlled by multiple biotic and abiotic factors. Although the response of these drivers to climate change will shape future recycling rates and their stoichiometry, their magnitude and variability are unaddressed by climate change projections, which means potentially important feedbacks on surface biogeochemistry are neglected.

Feasibility and first reports of the MATCH-R repeated biopsy trial at Gustave Roussy.

Unravelling the biological processes driving tumour resistance is necessary to support the development of innovative treatment strategies. We report the design and feasibility of the MATCH-R prospective trial led by Gustave Roussy with the primary objective of characterizing the molecular mechanisms of resistance to cancer treatments. The primary clinical endpoints consist of analyzing the type and frequency of molecular alterations in resistant tumours and compare these to samples prior to treatment.

DNA FISH Diagnostic Assay on Cytological Samples of Thyroid Follicular Neoplasms.

Although fine-needle aspiration cytology (FNAC) is helpful in determining whether thyroid nodules are benign or malignant, this distinction remains a cytological challenge in follicular neoplasms. Identification of genomic alterations in cytological specimens with direct and routine techniques would therefore have great clinical value. A series of 153 cases consisting of 72 and 81 histopathologically confirmed classic follicular adenomas (cFAs) and classic follicular thyroid carcinomas (cFTCs), respectively, was studied by means of different molecular techniques in three different cohorts of patients (pts).

Small Cell Carcinoma of the Ovary, Hypercalcemic Type (SCCOHT) beyond Mutations: A Comprehensive Genomic Analysis.

Small cell carcinoma of the ovary, hypercalcemic type (SCCOHT) is an aggressive malignancy that occurs in young women, is characterized by recurrent loss-of-function mutations in the gene, and for which effective treatments options are lacking. The aim of this study was to broaden the knowledge on this rare malignancy by reporting a comprehensive molecular analysis of an independent cohort of SCCOHT cases. We conducted Whole Exome Sequencing in six SCCOHT, and RNA-sequencing and array comparative genomic hybridization in eight SCCOHT.

Insights Into the Major Processes Driving the Global Distribution of Copper in the Ocean From a Global Model.

Copper (Cu) is an unusual micronutrient as it can limit primary production but can also become toxic for growth and cellular functioning under high concentrations. Cu also displays an atypical linear profile, which will modulate its availability to marine microbes across the ocean. Multiple chemical forms of Cu coexist in seawater as dissolved species and understanding the main processes shaping the Cu biogeochemical cycling is hampered by key knowledge gaps.

Association between FGFR1 copy numbers, MAP3K1 mutations, and survival in axillary node-positive, hormone receptor-positive, and HER2-negative early breast cancer in the PACS04 and METABRIC studies.

Purpose: Hormone receptor-positive (HR+) and human epidermal growth factor receptor 2 negative (HER2-) early breast cancer (BC) is the most prevalent BC subtype with substantial biological heterogeneity. Although clinicopathological (CP) characteristics have a clear prognostic value, additional biomarkers could refine survival prediction and guide treatment decision.

Methods: Copy number aberrations and somatic driver mutations were obtained with OncoScan CGH array and sequencing of 36 genes on HR+/HER2- node-positive early BC patients treated with chemotherapy from the PACS04 trial.

Added Value of Whole-Exome and Transcriptome Sequencing for Clinical Molecular Screenings of Advanced Cancer Patients With Solid Tumors.

Comprehensive genomic profiling using high-throughput sequencing brings a wealth of information, and its place in the clinical setting has been increasingly prominent. This review emphasizes the utility of whole-exome sequencing (WES) and transcriptome sequencing (RNAseq) in patient care and clinical research, based on published reports as well as our experience with the MOSCATO-01 (MOlecular Screening for CAncer Treatment Optimization) molecular triage trial at Gustave Roussy Cancer Center. In this trial, all contributive samples of patients with advanced solid tumors were analyzed prospectively with targeted gene sequencing (TGS) and comparative genomic hybridization.

Correction of the FSHD myoblast differentiation defect by fusion with healthy myoblasts.

Facioscapulohumeral dystrophy (FSHD) is a neuromuscular disease with a prevalence that could reach 1 in 8,000 characterized by progressive asymmetric muscle weakness. Myoblasts isolated from FSHD muscles exhibit morphological differentiation defects and show a distinct transcription profile. These abnormalities may be linked to the muscle weakness in FSHD patients.

Preclinical evaluation of dasatinib alone and in combination with cabozantinib for the treatment of diffuse intrinsic pontine glioma.

Background: Platelet-derived growth factor receptor A is altered by amplification and/or mutation in diffuse intrinsic pontine glioma (DIPG). We explored in vitro on new DIPG models the efficacy of dasatinib, a multi-tyrosine kinase inhibitor targeting this receptor.

Methods: Gene expression profiles were generated from 41 DIPGs biopsied at diagnosis and compared with the signature associated with sensitivity/resistance to dasatinib.

ITPR1 protects renal cancer cells against natural killer cells by inducing autophagy.

Clear cell renal cell carcinomas (RCC) frequently display inactivation of von Hippel-Lindau (VHL) gene leading to increased level of hypoxia-inducible factors (HIF). In this study, we investigated the potential role of HIF2α in regulating RCC susceptibility to natural killer (NK) cell-mediated killing. We demonstrated that the RCC cell line 786-0 with mutated VHL was resistant to NK-mediated lysis as compared with the VHL-corrected cell line (WT7).

Gene copy number variations in breast cancer of Sub-Saharan African women.

The goal of this study was CGH array profiling of breast cancer from Malian women in order to define differences with those from USA. CGH array was performed in 28 samples, 17 with a triple negative phenotype. The profiles were compared to those of 106 tumors from USA.

Array CGH and PIK3CA/AKT1 mutations to drive patients to specific targeted agents: a clinical experience in 108 patients with metastatic breast cancer.

Breast cancer includes high number of molecular entities targetable by specific agents. In this study, array CGH and PIK3CA/AKT1 mutations were used to drive patients into targeted therapy. A prospective molecular analysis was offered to metastatic breast cancer patients for whom samples were collected prospectively or retrospectively either from frozen or paraffin-embedded tissue.

Mesenchymal transition and PDGFRA amplification/mutation are key distinct oncogenic events in pediatric diffuse intrinsic pontine gliomas.

Diffuse intrinsic pontine glioma (DIPG) is one of the most frequent malignant pediatric brain tumor and its prognosis is universaly fatal. No significant improvement has been made in last thirty years over the standard treatment with radiotherapy. To address the paucity of understanding of DIPGs, we have carried out integrated molecular profiling of a large series of samples obtained with stereotactic biopsy at diagnosis.

Expression of miR-487b and miR-410 encoded by 14q32.31 locus is a prognostic marker in neuroblastoma.

Background: Combination of age at diagnosis, stage and MYCN amplification stratifies neuroblastoma into low-risk and high-risk. We aimed to establish whether a microRNA (miRNA) signature could be associated with prognosis in both groups.

Methods: Microarray expression profiling of human miRNAs and quantitative reverse-transcriptase PCR of selected miRNAs were performed on a preliminary cohort of 13 patients.

Chromosomal minimal critical regions in therapy-related leukemia appear different from those of de novo leukemia by high-resolution aCGH.

Therapy-related acute leukemia (t-AML), is a severe complication of cytotoxic therapy used for primary cancer treatment. The outcome of these patients is poor, compared to people who develop de novo acute leukemia (p-AML). Cytogenetic abnormalities in t-AML are similar to those found in p-AML but present more frequent unfavorable karyotypes depending on the inducting agent.

hSMG-1 is a granzyme B-associated stress-responsive protein kinase.

Granzyme B plays a key role in cell-mediated programmed cell death. We previously demonstrated that p53 is a functional determinant in the granzyme B-induced cytotoxic T-lymphocyte response. However, the pathways leading to activation of p53 by granzyme B remain incompletely understood.

High resolution genome-wide analysis of chromosomal alterations in Burkitt's lymphoma.

Additional chromosomal abnormalities are currently detected in Burkitt's lymphoma. They play major roles in the progression of BL and in prognosis. The genes involved remain elusive.

Synergistic proapoptotic effects of the two tyrosine kinase inhibitors pazopanib and lapatinib on multiple carcinoma cell lines.

Pazopanib and lapatinib are two tyrosine kinase inhibitors that have been designed to inhibit the VEGF tyrosine kinase receptors 1, 2 and 3 (pazopanib), and the HER1 and HER2 receptors in a dual manner (lapatinib). Pazopanib has also been reported to mediate inhibitory effect on a selected panel of additional tyrosine kinases such as PDGFR and c-kit. Here, we report that pazopanib and lapatinib act synergistically to induce apoptosis of A549 non-small-cell lung cancer cells.

The cooperative induction of hypoxia-inducible factor-1 alpha and STAT3 during hypoxia induced an impairment of tumor susceptibility to CTL-mediated cell lysis.

Hypoxia is an essential component of tumor microenvironment. In this study, we investigated the influence of hypoxia (1% PO(2)) on CTL-mediated tumor cell lysis. We demonstrate that exposure of target tumor cells to hypoxia has an inhibitory effect on the CTL clone (Heu171)-induced autologous target cell lysis.

Molecular characterization of breast cancer with high-resolution oligonucleotide comparative genomic hybridization array.

Purpose: We used high-resolution oligonucleotide comparative genomic hybridization (CGH) arrays and matching gene expression array data to identify dysregulated genes and to classify breast cancers according to gene copy number anomalies.

Experimental Design: DNA was extracted from 106 pretreatment fine needle aspirations of stage II-III breast cancers that received preoperative chemotherapy. CGH was done using Agilent Human 4 x 44K arrays.