A5023012572- Cancer Genomics and Diagnostics
- Sarcoma Diagnosis and Treatment
- Cancer, Hypoxia, and Metabolism
- Cancer-related molecular mechanisms research
- RNA modifications and cancer
- Neuroblastoma Research and Treatments
- Cancer Cells and Metastasis
- RNA Research and Splicing
- Virus-based gene therapy research
- Pleural and Pulmonary Diseases
- Cancer Diagnosis and Treatment
- Orthopedic Infections and Treatments
- Single-cell and spatial transcriptomics
- ATP Synthase and ATPases Research
- Cancer Research and Treatments
- Radiopharmaceutical Chemistry and Applications
- Cancer-related Molecular Pathways
- CAR-T cell therapy research
- Immune cells in cancer
- Molecular Biology Techniques and Applications
- Genetic factors in colorectal cancer
- Lipid metabolism and disorders
- Cytokine Signaling Pathways and Interactions
- Cancer, Lipids, and Metabolism
- Radiomics and Machine Learning in Medical Imaging
Hôpital Pellegrin
2025
Médecins du Monde
2025
Hôpital Paul-Brousse
2025
Nationwide Children's Hospital
2012-2024
The Ohio State University
2013
Robert Koch Institute
2009
Recent studies have shown the importance of dynamic tumor microenvironment (TME) in high-grade gliomas (HGGs). In particular, myeloid cells are known to mediate immunosuppression glioma; however, it is still unclear if play a role low-grade glioma (LGG) malignant progression. Here, we investigate cellular heterogeneity TME using single-cell RNA sequencing murine model that recapitulates progression LGG HGG. LGGs show increased infiltrating CD4
Osteosarcoma (OS), a malignant tumor of bone, kills through aggressive metastatic spread almost exclusively to the lung. Mechanisms driving this tropism for lung tissue remain unknown, though likely invoke specific interactions between cells and other within niche. Aberrant overexpression ΔNp63 in OS directly drives production IL-6 CXCL8. All these factors were expressed at higher levels metastases than matched primary tumors from same patients. Expression cell lines correlated strongly with...
Abstract Background Tumors are complex tissues containing collections of phenotypically diverse malignant and nonmalignant cells. We know little the mechanisms that govern heterogeneity tumor cells nor role plays in overcoming stresses, such as adaptation to different microenvironments. Osteosarcoma is an ideal model for studying these mechanisms—it exhibits widespread inter- intra-tumoral heterogeneity, predictable patterns metastasis, a lack clear targetable driver mutations. Understanding...
Ewing sarcoma (EWS) is the second most common and aggressive type of metastatic bone tumor in adolescents young adults. There unmet medical need to develop test novel pharmacological targets therapies treat EWS. Here, we found that EWS expresses high levels a p53 isoform, delta133p53. We further determined aberrant expression delta133p53 induced HGF secretion resulting growth metastasis. Thereafter, evaluated targeting tumors with receptor neutralizing antibody (AMG102) preclinical studies....
Osteosarcoma is an aggressive malignancy characterized by high genomic complexity. Identification of few recurrent mutations in protein coding genes suggests that somatic copy-number aberrations (SCNA) are the genetic drivers disease. Models around instability conflict-it unclear whether osteosarcomas result from pervasive ongoing clonal evolution with continuous optimization fitness landscape or early catastrophic event followed stable maintenance abnormal genome. We address this question...
Lung metastasis is responsible for nearly all deaths caused by osteosarcoma, the most common pediatric bone tumor. How malignant cells coerce lung microenvironment to support metastatic growth unclear. The purpose of this study identify metastasis-specific therapeutic vulnerabilities delineating cellular and molecular mechanisms underlying osteosarcoma niche formation.
<p>scRNA-seq marker expression and protein level validation of macrophage epithelial cell enrichment</p>
<p>Niche-wide changes in target signaling pathway activity with immediate and delayed nintedanib</p>
<p>Immediate vs delayed treatment, tumor burden-based randomization</p>
<div>AbstractPurpose:<p>Lung metastasis is responsible for nearly all deaths caused by osteosarcoma, the most common pediatric bone tumor. How malignant cells coerce lung microenvironment to support metastatic growth unclear. The purpose of this study identify metastasis-specific therapeutic vulnerabilities delineating cellular and molecular mechanisms underlying osteosarcoma niche formation.</p>Experimental Design:<p>Using single-cell RNA sequencing, we characterized...
<p>Chronic wound epithelial cells (KRT8+) accumulate in human patient osteosarcoma lung metastasis</p>
<p>Unaffected thick tissue epithelial z-stack</p>
<p>Metastasis thick tissue epithelial z-stack</p>
<p>Tumor cell-intrinsic effects of nintedanib</p>
<p>K7M2 shows evidence of acute alveolar injury during osteosarcoma metastasis</p>
<p>Mechanistic and pharmacodynamic effects of nintedanib</p>
<p>Ligand-Receptor-Target (NicheNET) gene expression analysis</p>
Abstract The tumor suppressor gene p53 and its family members p63/p73 are critical determinants of tumorigenesis. ΔNp63 is a splice variant p63, which lacks the N-terminal transactivation domain. It thought to antagonize p53-, p63-, p73-dependent translation, thus blocking their activity. In our studies pediatric solid tumors neuroblastoma osteosarcoma, we find overexpression ΔNp63; however, there no correlation expression with mutation status. Our data suggest that itself endows cells...
The pre-metastatic niche (PMN) represents an abnormal microenvironment devoid of cancer cells, but favoring tumor growth. Little is known about the mechanisms that generate PMN or their effects on host cells within metastasis-prone organs. Here, we investigated by using spontaneous metastatic models whether lung epithelial are essential for primary induced neutrophil recruitment in and subsequently initiating formation osteosarcoma. We found serum levels ANGPTL2 osteosarcoma patients...
Glioblastoma (GBM) remains one of the least successfully treated cancers. It is essential to understand basic biology this lethal disease and investigate novel pharmacological targets treat GBM. The aims study were determine biological consequences elevated expression ΔNp73, an N-terminal truncated isoform TP73, evaluate targeting its downstream mediators, angiopoietin 1 (ANGPT1)/tunica interna endothelial cell kinase 2 (Tie2) axis, by using a highly potent, orally available small-molecule...
p63 is a structural homolog within the 53 family encoding two isoforms, ΔNp63 and TAp63. The oncogenic activity of has been demonstrated in multiple cancers, however underlying mechanisms that contribute to tumorigenesis are poorly characterized. Osteosarcoma (OSA) most common primary bone tumor dogs, exhibiting clinical behavior molecular biology essentially identical its human counterpart. purpose this study was evaluate potential contribution canine OSA. As by qRT-PCR, nearly all OSA cell...
Oncolytic viruses, modified for tumor-restricted infection, are a promising cancer immunotherapeutic, yet much remains to be understood about factors driving their activity and outcome in the tumor microenvironment. Here, we report that oncolytic herpes simplex virus C134, previously found exert T cell-dependent efficacy mouse models of glioblastoma, exerts cell-independent medulloblastoma, indicating this uses different mechanisms tumors. We investigated C134's behavior medulloblastomas,...
We previously reported that the DNA alkylator and transcriptional-blocking chemotherapeutic agent trabectedin enhances oncolytic herpes simplex viroimmunotherapy in human sarcoma xenograft models, though mechanism remained to be elucidated. Here we report disrupts intrinsic cellular anti-viral response which increases viral transcript spread throughout tumor cells. also extended our synergy findings syngeneic murine are poorly susceptible virus infection. In absence of robust replication,...