A5062042608- Cancer Genomics and Diagnostics
- Lung Cancer Treatments and Mutations
- Colorectal Cancer Treatments and Studies
- Genomic variations and chromosomal abnormalities
- Cancer Mechanisms and Therapy
- Immune Cell Function and Interaction
- Cancer therapeutics and mechanisms
- Radiomics and Machine Learning in Medical Imaging
- Cancer-related Molecular Pathways
- Immunotherapy and Immune Responses
- Extracellular vesicles in disease
- Cell death mechanisms and regulation
- Immune cells in cancer
- RNA modifications and cancer
- Cancer Research and Treatments
- Epigenetics and DNA Methylation
- Cancer, Hypoxia, and Metabolism
- Bladder and Urothelial Cancer Treatments
- Glioma Diagnosis and Treatment
- Gene expression and cancer classification
- Congenital heart defects research
- Phagocytosis and Immune Regulation
- Ubiquitin and proteasome pathways
- Neuroblastoma Research and Treatments
- PI3K/AKT/mTOR signaling in cancer
Weatherford College
2022
Institut Gustave Roussy
2009-2020
Université Paris-Saclay
2012-2020
Inserm
2003-2020
Centre National de la Recherche Scientifique
2014-2020
Centre Jean Perrin
2018
UniCancer Group
2018
Université Paris Cité
2006-2014
Laboratoire de Vectorologie et Thérapeutiques Anticancéreuses
2014
Karolinska Institutet
2014
High-throughput genomic analyses may improve outcomes in patients with advanced cancers. MOSCATO 01 is a prospective clinical trial evaluating the benefit of this approach. Nucleic acids were extracted from fresh-frozen tumor biopsies and analyzed by array comparative hybridization, next-generation sequencing, RNA sequencing. The primary objective was to evaluate as measured percentage presenting progression-free survival (PFS) on matched therapy (PFS2) 1.3-fold longer than PFS prior (PFS1)....
Abstract Purpose: We used high-resolution oligonucleotide comparative genomic hybridization (CGH) arrays and matching gene expression array data to identify dysregulated genes classify breast cancers according copy number anomalies. Experimental Design: DNA was extracted from 106 pretreatment fine needle aspirations of stage II-III that received preoperative chemotherapy. CGH done using Agilent Human 4 × 44K arrays. Gene generated with Affymetrix U133A chips also available on 103 patients....
Diffuse intrinsic pontine glioma (DIPG) is one of the most frequent malignant pediatric brain tumor and its prognosis universaly fatal. No significant improvement has been made in last thirty years over standard treatment with radiotherapy. To address paucity understanding DIPGs, we have carried out integrated molecular profiling a large series samples obtained stereotactic biopsy at diagnosis. While chromosomal imbalances did not distinguish DIPG supratentorial tumors on CGHarrays, gene...
Lorlatinib is a third-generation anaplastic lymphoma kinase (ALK) tyrosine inhibitor with proven efficacy in patients ALK-rearranged lung cancer previously treated first- and second-generation ALK inhibitors. Beside compound mutations the domain, other resistance mechanisms driving lorlatinib remain unknown. We aimed to characterize of occurring design new therapeutic strategies this setting.Resistance were investigated 5 resistant lorlatinib. Longitudinal tumor biopsies studied using...
Abstract Hypoxia is an essential component of tumor microenvironment. In this study, we investigated the influence hypoxia (1% PO2) on CTL-mediated cell lysis. We demonstrate that exposure target cells to has inhibitory effect CTL clone (Heu171)-induced autologous Such inhibition correlates with hypoxia-inducible factor-1α (HIF-1α) induction but not associated alteration reactivity as revealed by granzyme B polarization or morphological change. Western blot analysis indicates although had no...
Abstract Clear cell renal carcinomas (RCC) frequently display inactivation of von Hippel-Lindau (VHL) gene leading to increased level hypoxia-inducible factors (HIF). In this study, we investigated the potential role HIF2α in regulating RCC susceptibility natural killer (NK) cell–mediated killing. We demonstrated that line 786-0 with mutated VHL was resistant NK-mediated lysis as compared VHL-corrected (WT7). This resistance found require stabilization. On basis global expression profiling...
Combination of age at diagnosis, stage and MYCN amplification stratifies neuroblastoma into low-risk high-risk. We aimed to establish whether a microRNA (miRNA) signature could be associated with prognosis in both groups. Microarray expression profiling human miRNAs quantitative reverse-transcriptase PCR selected were performed on preliminary cohort 13 patients. Results validated an independent 214 The relationship between miRNA the overall or disease-free survival was analysed total 227...
Additional chromosomal abnormalities are currently detected in Burkitt's lymphoma. They play major roles the progression of BL and prognosis. The genes involved remain elusive. A whole-genome oligonucleotide array CGH analysis correlated with karyotype FISH was performed a set 27 lymphoma-derived cell lines primary tumors. More than half 145 CNAs<2 Mb were mapped to Mendelian CNVs, including GSTT1, glutathione s-transferase BIRC6, an anti-apoptotic protein, possibly predisposing some...
Platelet-derived growth factor receptor A is altered by amplification and/or mutation in diffuse intrinsic pontine glioma (DIPG). We explored vitro on new DIPG models the efficacy of dasatinib, a multi-tyrosine kinase inhibitor targeting this receptor. Gene expression profiles were generated from 41 DIPGs biopsied at diagnosis and compared with signature associated sensitivity/resistance to dasatinib. panel 12 cell lines established biopsy diagnosis, serially passaged, characterized gene...
Small cell carcinoma of the ovary, hypercalcemic type (SCCOHT) is an aggressive malignancy that occurs in young women, characterized by recurrent loss-of-function mutations SMARCA4 gene, and for which effective treatments options are lacking. The aim this study was to broaden knowledge on rare reporting a comprehensive molecular analysis independent cohort SCCOHT cases. We conducted Whole Exome Sequencing six SCCOHT, RNA-sequencing array comparative genomic hybridization eight SCCOHT....
To investigate tumor resistance to T cell lysis, a resistant variant was selected after specific cytolytic lymphocytes (CTL) selection pressure. Although the triggered perforin and granzyme B transcription in CTLs, as well their degranulation, it exhibited dramatic cytotoxic killing. It also displayed strong morphological changes with alterations of actin cytoskeleton. Electron microscopy analysis revealed loosen interaction between CTLs despite formation apparently normal conjugates....
Unravelling the biological processes driving tumour resistance is necessary to support development of innovative treatment strategies. We report design and feasibility MATCH-R prospective trial led by Gustave Roussy with primary objective characterizing molecular mechanisms cancer treatments. The clinical endpoints consist analyzing type frequency alterations in resistant tumours compare these samples prior treatment. Patients experiencing disease progression after an initial partial...
Abstract We previously characterized several tumor-specific T cell clones from PBL and tumor-infiltrating lymphocytes of a lung cancer patient with identical TCR rearrangements similar lytic potential, but different antitumor response. A role the inhibitory molecule CD5 to impair reactivity peripheral cells against tumor was found be involved in this process. In report, we demonstrate that also controls susceptibility specific activation-induced death (AICD) triggered by tumor. Using panel...
2512 Background: Characterization of the genomic alterations (GA) that could drive tumor growth an individual patient (pt) is now critical to better select targeted therapies in phase I trials. Methods: Pts with advanced solid tumors, who failed at least one line standard therapy, were offered on-purpose biopsy for molecular characterization. Biopsies mainly obtained using 18G needles under CT or ultra-sound control, from metastatic primary sites. DNA extracted fresh biopsies was analyzed by...
In this study we investigated the involvement of p53 in cytotoxic T-lymphocyte (CTL)-induced tumor target cell killing mediated by perforin/granzymes pathway. For purpose used a human CTL clone (LT12) that kills its autologous melanoma cells (T1), harboring wild type p53. We demonstrated initially LT12 T1 perforin/granzymes-dependent manner. Confocal microscopy and Western blot analysis indicated conjugate formed between resulted rapid cytoplasmic accumulation activation cells. Cytotoxic...
Therapy-related acute leukemia (t-AML), is a severe complication of cytotoxic therapy used for primary cancer treatment. The outcome these patients poor, compared to people who develop de novo (p-AML). Cytogenetic abnormalities in t-AML are similar those found p-AML but present more frequent unfavorable karyotypes depending on the inducting agent. Losses chromosome 5 or 7 observed after alkylating agents while balanced translocations topoisomerase II inhibitors. This study using high...
Natural cytotoxicity receptors and NKG2D correspond to major activating involved in triggering of tumor cell lysis by human NK cells. In this report, we investigated the expression ligands (NKG2DLs), MHC class I-related chain (MIC) A, MICB UL16-binding proteins 1, 2 3, on a panel non-small-cell lung carcinoma lines, analyzed their role susceptibility lysis. Although adenocarcinoma (ADC) cells expressed heterogeneous levels NKG2DLs, they were often resistant cell-mediated killing. Resistance...
Abstract In this study, we have investigated the mechanisms used by wild-type p53 (wtp53) to potentiate tumor cell susceptibility CTL-mediated death. We report that wtp53 restoration in a human lung carcinoma line Institut Gustave Roussy (IGR)-Heu, displaying mutated p53, resulted up-regulation of Fas/CD95 receptor expression associated with an increase sensitivity autologous CTL clone, Heu127. However, when IGR-Heu cells were transfected Fas cDNA, no potentiation Heu127-mediated lysis was...
Abstract Background: The widespread use of high-throughput molecular techniques has allowed the identification recurrent and actionable traits across various tumor types. Translating these approaches to bedside may guide decision-making for cancer patients candidates early clinical trials. Methods: Patients with advanced solid tumors, refered our drug development department (DITEP), were prospectively enrolled in a prospective screening program at Gustave Roussy (France). CT-Scan or...
Abstract Inactivation of p53 has been implicated in many types tumors particularly non-small cell lung carcinoma, one the most common cancers which mutation frequently identified. The aim this study was to investigate influence status on regulation tumor susceptibility specific CTL-mediated death. For purpose, we used a cytotoxic T lymphocyte clone, Heu127, able lyse human autologous carcinoma line, IGR-Heu, HLA-A2-restricted manner. Direct genomic DNA sequencing revealed that IGR-Heu...
Facioscapulohumeral dystrophy (FSHD) is a neuromuscular disease with 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 distinct transcription profile. These abnormalities may be linked to the weakness patients. We have tested whether fusion of myoblasts primary healthy individuals correct defects. Our results number hybrid myotubes normal phenotype...