A5069717035- Cancer-related gene regulation
- Sarcoma Diagnosis and Treatment
- CAR-T cell therapy research
- Cancer Genomics and Diagnostics
- Protein Degradation and Inhibitors
- Uterine Myomas and Treatments
- Radiomics and Machine Learning in Medical Imaging
- Endometrial and Cervical Cancer Treatments
- Gastrointestinal Tumor Research and Treatment
- Genetic factors in colorectal cancer
- Peptidase Inhibition and Analysis
- Cardiovascular Effects of Exercise
- Viral Infectious Diseases and Gene Expression in Insects
- Insect and Pesticide Research
- Tuberous Sclerosis Complex Research
- Adenosine and Purinergic Signaling
- Parkinson's Disease Mechanisms and Treatments
- Endometriosis Research and Treatment
- Vascular Tumors and Angiosarcomas
- Receptor Mechanisms and Signaling
- Cancer-related molecular mechanisms research
- Colorectal Cancer Treatments and Studies
- Cancer Cells and Metastasis
- CRISPR and Genetic Engineering
- Muscle Physiology and Disorders
Institut Bergonié
2017-2024
Inserm
2018-2024
Université de Bordeaux
2023-2024
Gene Therapy Laboratory
2021-2023
Translational Research in Gene Therapy
2021-2023
Selective KRAS
Abstract Our objective was to capture subgroups of soft-tissue sarcoma (STS) using handcraft and deep radiomics approaches understand their relationship with histopathology, gene-expression profiles, metastatic relapse-free survival (MFS). We included all consecutive adults newly diagnosed locally advanced STS ( N = 225, 120 men, median age: 62 years) managed at our reference center between 2008 2020, contrast-enhanced baseline MRI. After MRI postprocessing, segmentation, reproducibility...
Abstract Background Soft-tissue sarcomas (STS) represent a heterogeneous group of rare tumors including more than 70 different histological subtypes. High throughput molecular analysis (next generation sequencing exome [NGS]) is unique opportunity to identify driver mutations that can change the usual one-size-fits-all treatment paradigm patient-driven therapeutic strategy. The primary objective MULTISARC trial assess whether NGS be conducted for large proportion metastatic STS participants...
Inhibition of ChK1 appears as a promising strategy for selectively potentiate the efficacy chemotherapeutic agents in G1 checkpoint-defective tumor cells such those that lack functional p53 protein. The pathway is commonly dysregulated soft-tissue sarcomas (STS) through mutations affecting TP53 or MDM2 amplification. GDC-0575 selective ATP-competitive inhibitor CHK1.We have performed systematic screening panel 10 STS cell lines by combining treatment with chemotherapy. Cell proliferation,...
Leiomyosarcoma (LMS) is one of the most frequent soft tissue sarcoma subtypes and characterized by a consistent deregulation PI3K/mTOR pathway. Cancer stem cells (CSCs) have been poorly studied in sarcomas. In this study, we aimed to evaluate association between CSCs, outcome LMS patients, resistance pathway inhibition. We investigated relationships aldehyde dehydrogenase 1 (ALDH1) expression, cancer cell marker, patients two independent cohorts. assessed impact CSCs inhibition using lines,...
Lymph node metastasis is determinant in the prognosis and treatment of endometrioid endometrial cancer (EEC) but risk-benefit balance surgical lymph staging remains controversial.Describe pathways associated with metastases EEC detected by whole RNA sequencing.RNA-sequencing was performed on a retrospective series 30 non-metastatic EEC. N+ N- patients were matched for tumoral size, grade myometrial invasion.Twenty-eight EECs analyzable (16 12 N-). Bioinformatics Unsupervised analysis...
Abstract Introduction: STS are mostly prognosticated through nomograms relying on age, size, histotype and grade. Radiomics approaches, complemented with deep-learning, deep-radiomics gene-expression profiling, could help understanding the bridge between radiophenotypes molecular features provide more efficient prognostic tools. Our goals were to investigate correlations imaging transcriptomics patterns, develop supervised models for patients. Methods: We included all consecutive adult...
Patients with advanced soft-tissue sarcomas (STS) have few therapeutic options. Protein arginine methyltransferase 5 (PRMT5), an anticancer target, has been extensively investigated in recent years epithelial tumors. To date, no data related to the biological role of PRMT5 inhibition and its potential effect as a treatment STS reported.To investigate targeting STS, we first evaluated prognostic value expression two different cohorts patients STS. We then used potent selective GSK3326595...
<div>Abstract<p>Patients with advanced soft-tissue sarcomas (STS) have few therapeutic options. Protein arginine methyltransferase 5 (PRMT5), an anticancer target, has been extensively investigated in recent years epithelial tumors. To date, no data related to the biological role of PRMT5 inhibition and its potential effect as a treatment STS reported.</p><p>To investigate targeting STS, we first evaluated prognostic value <i>PRMT5</i> expression two...
<p>PRMT5 inhibition impairs glycolysis in STSs. <b>A,</b> Western blot analysis showing key proteins involved glycolysis. Sarcoma cell lines were treated for 10 days without or with GSK595 at the IC<sub>80</sub> before protein extraction. <b>B,</b> Quantitation of bands (<i>n</i> = 2 more). <b>C</b> and <b>D,</b> Relative glucose uptake lactate production measured by colorimetric assay after treatment...
<div>Abstract<p>Patients with advanced soft-tissue sarcomas (STS) have few therapeutic options. Protein arginine methyltransferase 5 (PRMT5), an anticancer target, has been extensively investigated in recent years epithelial tumors. To date, no data related to the biological role of PRMT5 inhibition and its potential effect as a treatment STS reported.</p><p>To investigate targeting STS, we first evaluated prognostic value <i>PRMT5</i> expression two...
<p>Antitumor effects of PRMT5 inhibition on STSs. <b>A,</b> Assessment cell viability with inhibitor GSK3226595 (GSK595) in seven STS lines (with TP53 deleted or not) as determined by MTT assay (<i>n</i> = 3 more). Cells were treated a range increasing concentrations drug for 10 days and the IC<sub>50</sub> was calculated GraphPad Prism software. <b>B,</b> Western blot analysis showing SDMA, p53, p21 protein expression four after GSK595...
<p>Transcriptome analysis of PRMT5 inhibition in STSs. <b>A,</b> Volcano plot showing differential gene expression after RNA-seq with the IB111 cell line that was untreated or treated GSK595 for 10 days at IC<sub>50</sub> biological triplicates. A total 556 genes (green dots) and 486 (red were significantly downregulated upregulated treatment. <b>B,</b> Pathway shown A. MSigDB FGSEA used to identify hallmark pathways Gene Ontology (GO) process terms...
<p>Suppl Fig 1 showing the PRMT5 inhibition effect on expression, cell cycle phases and apoptosis</p>
<p>Antitumor effects of PRMT5 inhibition on STSs. <b>A,</b> Assessment cell viability with inhibitor GSK3226595 (GSK595) in seven STS lines (with TP53 deleted or not) as determined by MTT assay (<i>n</i> = 3 more). Cells were treated a range increasing concentrations drug for 10 days and the IC<sub>50</sub> was calculated GraphPad Prism software. <b>B,</b> Western blot analysis showing SDMA, p53, p21 protein expression four after GSK595...
<p>supplementary methods for apoptosis and cell cycle analysis Western blot</p>
<p>PRMT5 inhibition impairs glycolysis in STSs. <b>A,</b> Western blot analysis showing key proteins involved glycolysis. Sarcoma cell lines were treated for 10 days without or with GSK595 at the IC<sub>80</sub> before protein extraction. <b>B,</b> Quantitation of bands (<i>n</i> = 2 more). <b>C</b> and <b>D,</b> Relative glucose uptake lactate production measured by colorimetric assay after treatment...