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siRNA, overexpression, constitutive or inducible
In vitro & in vivo validation
Phenotypic and functional assays
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300 tumor cell lines
Fresh primary tumor samples
Cytotoxicity assays (MTS, SRB, BrDU)
Clonogenicity assays
FACS (apoptosis, cell cycle…)
51Cr release assay (ADCC, CDC)
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Preclinical formulation
MTD / MTTD (drug alone or combination)
PK (HPLC-MS / MS, ICP-MS, ELISA, radiolabeled)
Subcutaneous models
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Orthotopic & metastatic models
Transgenic & chemoinduced models
Xenografted Nude rats
Optimization of administration schedule
Combination with reference drugs
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Angiogenesis (functional histology & IHC)
Hypoxia quantification
Immunological response characterization (cytokines, cellular populations’ activation…)
Immune cells infiltration in tumors (IHC)
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µMRI (4.7T) under SPF conditions (morphology, Ktrans, BOLD, ADC, VSI…)
µPET (FDG, FLT, FMISO…)
Optimization of combination (pharmacological active dose, schedule, sequences, delays…)
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Nude rats
Correlation between PD, PK, mechanistic effect, toxicity (hemato & neuro) and metabolism
Use of classical techniques or imaging techniques
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Pierre Fumoleau, MD
4 MDs, 5CRAs, 1 nurse
8 beds
Clinical MRI and PET
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