A5085104401- Ovarian cancer diagnosis and treatment
- Genetic factors in colorectal cancer
- DNA Repair Mechanisms
- PARP inhibition in cancer therapy
- Cancer Immunotherapy and Biomarkers
- Cancer Genomics and Diagnostics
- CAR-T cell therapy research
- Genetic and Clinical Aspects of Sex Determination and Chromosomal Abnormalities
- Animal Genetics and Reproduction
- FOXO transcription factor regulation
- Reproductive Biology and Fertility
- Cancer Mechanisms and Therapy
- Sexual Differentiation and Disorders
- Chromatin Remodeling and Cancer
- Endometrial and Cervical Cancer Treatments
- Genetic and phenotypic traits in livestock
- Sperm and Testicular Function
- BRCA gene mutations in cancer
- Birth, Development, and Health
- Monoclonal and Polyclonal Antibodies Research
- Cancer-related molecular mechanisms research
- Immune Cell Function and Interaction
- Immunotherapy and Immune Responses
- Infant Nutrition and Health
- Cancer Research and Treatments
Pfizer (France)
2024
Université Paris-Saclay
2017-2023
Inserm
2015-2023
Hôpital Laveran
2023
Boehringer Ingelheim (Germany)
2020-2022
Institut Gustave Roussy
2015-2020
Centre National de la Recherche Scientifique
2013-2020
Institut de Recherche en Santé, Environnement et Travail
2020
Translational Research in Oncology
2016
Université Paris-Sud
2016
The elevated levels of somatic copy-number alterations (SCNAs) in a subset high-risk endometrial cancers are suggestive defects pathways governing genome integrity. We sought to assess the prevalence homologous recombination deficiency (HRD) and its association with histopathologic molecular characteristics.
FOXL2 is a lineage determining transcription factor in the ovary, but its direct targets and modes of action are not fully characterized. In this study, we explore five nuclear receptors murine primary follicular cells. We found that required for normal gene regulation by steroid receptors, show estrogen receptor beta (ESR2) main vector estradiol signaling these Moreover, directly modulates Esr2 expression through newly identified intronic element. Interestingly, repressed testis-determining...
Abstract Inactivating mutations in SMARCA4 ( BRG1 ), a key SWI/SNF chromatin remodelling gene, underlie small cell carcinoma of the ovary, hypercalcemic type (SCCOHT). To reveal its druggable vulnerabilities, we perform kinase-focused RNAi screens and uncover that SMARCA4-deficient SCCOHT cells are highly sensitive to inhibition cyclin-dependent kinase 4/6 (CDK4/6). loss causes profound downregulation cyclin D1, which limits CDK4/6 activity leads vitro vivo susceptibility inhibitors. patient...
The gonad arises from the thickening of coelomic epithelium and then commits into sex determination process. Testis differentiation is activated by expression Y-linked gene Sry, which promotes cell proliferation Sertoli cells, supporting cells testis. In absence Sry (XX individuals), activation WNT/CTNNB1 signalling, via upregulation Rspo1 Wnt4, ovarian differentiation. However, Wnt4 are expressed in early undifferentiated both sexes, Axin2-lacZ, a reporter canonical region E11.5 gonadal...
Ovarian granulosa cell tumors are the most common sex-cord stromal and have juvenile (JGCTs) adult forms. In a previous study we reported occurrence of activating somatic mutations Gαs, which transduces mitogenic signals, in 30% analyzed JGCTs.We searched for alterations other proteins involved ovarian signaling. We focused on PI3K-AKT axis. As found AKT1, subcellular localization mutated performed functional explorations using Western-blot luciferase assays.We detected in-frame duplications...
In vertebrates, 2 main genetic pathways have been shown to regulate ovarian development. Indeed, a loss of function mutations in <i>Rspo1</i> and <i>Foxl2</i> promote partial female-to-male sex reversal. mice, it has that the secreted protein RSPO1 is involved differentiation transcription factor FOXL2 required for follicular formation. Here, we analysed potential interactions between these while expression seems be independent <i>Foxl2 </i>up-regulation,...
Juvenile granulosa cell tumors (JGCTs) of the ovary are pediatric neoplasms representing 5% all (GCTs). Most GCTs adult type (AGCTs) and bear a mutation in FOXL2 gene. The molecular basis JGCTs is poorly understood, although mutations GNAS gene have been reported. We detected in-frame duplications within oncogene AKT1 >60% studied. Here, to evaluate functional impact these existence potential co-driver alterations, we sequenced transcriptome four compared them with control transcriptomes. A...
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....
The rabbit is an attractive species for the study of gonad differentiation because its 31-day long gestation, timing female meiosis around birth and 15-day delay between gonadal switch onset in female. expression a series genes was thus determined by qPCR during foetal life until adulthood, completed histological analysis whenever possible immunohistological one. Interesting gene profiles were recorded. Firstly, peak SRY that observed early differentiated XY gonads numerous mammals also seen...
Many patients with cancer do not benefit from currently approved immune checkpoint inhibitors (ICIs), suggesting that additional immunomodulation of the immunosuppressive tumor microenvironment (TME) is required. MTL-CCAAT enhancer-binding protein alpha (CEBPA) specifically upregulates expression master myeloid transcription factor, CEBPA, relieving myeloid-driven immunosuppression. Here, we report safety, tolerability, pharmacokinetics, and efficacy MTL-CEBPA in combination pembrolizumab...
Abstract Despite some impressive clinical results with immune checkpoint inhibitors, the majority of patients cancer do not respond to these agents, in part due immunosuppressive mechanisms tumor microenvironment. High levels adenosine tumors can suppress cell function, and strategies target pathway involved its production have emerged. CD73 is a key enzyme production. This led us identify novel humanized antagonistic antibody, mAb19, distinct binding properties. mAb19 potently inhibits...
Abstract Axicabtagene ciloleucel (axi-cel), an autologous anti-CD19 chimeric antigen receptor (CAR) T-cell therapy, was approved for patients with relapsed or refractory large B-cell lymphoma (LBCL) after two more lines of systemic therapy (ZUMA-1, NCT02348216), as well those to relapsing within 12 months first-line chemoimmunotherapy (ZUMA-7, NCT03391466). Recent molecular classifications LBCL based on genetic factors shown associate response R-CHOP and other chemo-immunotherapy standard...
Molecular profiling is considered a standard of care in advanced NSCLC. A comprehensive next-generation sequencing panel can discover somatic or germline BRCA1/2 mutations that are new druggable molecular alterations. However, the phenotypic and potential therapeutic relevance mutation NSCLC remains poorly defined.From April 2014 to March 2017, 600 newly diagnosed, EGFR/ALK negative patients with were enrolled SAFIR02-Lung trial. was done at study entry on archival tissue frozen collected...
Advanced-stage gastrointestinal cancers represent a high unmet need requiring new effective therapies. We investigated the antitumor activity of novel T cell-engaging antibody (B7-H6/CD3 ITE) targeting B7-H6, tumor-associated antigen that is expressed in tumors.Membrane proteomics and IHC analysis identified B7-H6 as tumor tissues with no to very little expression normal tissues. The mode action B7-H6/CD3 ITE was evaluated vitro coculture assays, humanized mouse models, colorectal cancer...
Polled and Multisystemic Syndrome (PMS) is a novel developmental disorder occurring in the progeny of single bull. Its clinical spectrum includes polledness (complete agenesis horns), facial dysmorphism, growth delay, chronic diarrhea, premature ovarian failure, variable neurological cardiac anomalies. PMS also characterized by deviation sex-ratio, suggesting male lethality during pregnancy. Using Mendelian error mapping whole-genome sequencing, we identified 3.7 Mb deletion on paternal...
FOXL2, a winged-helix/forkhead domain transcription factor, is key gene involved in the differentiation and biological functions of ovary. In recent transcriptomic analysis, we found that FOXL2 expression bovine caruncular endometrium was different from intercaruncular endometrium. order to gain new insights into this tissue, determined factor during estrous cycle establishment pregnancy cattle. The endometrial did not vary maternal recognition (Days 16–20). Using an vivo model primary cell...