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Christen T.,French Institute of Health and Medical Research | Christen T.,Stanford University | Lemasson B.,French Institute of Health and Medical Research | Lemasson B.,Oncodesign | And 5 more authors.
Radiology | Year: 2012

Purpose: To analyze the contribution of the transverse relaxation parameter (T2), macroscopic field inhomogeneities (ΔB 0), and blood volume fraction (BVf) to blood oxygen level-dependent (BOLD)-based magnetic resonance (MR) measurements of blood oxygen saturation (SO 2) obtained in a brain tumor model. Materials and Methods: This study was approved by the local committee for animal care and use. Experiments were performed in accordance with permit 380 820 from the French Ministry of Agriculture. The 9L gliosarcoma cells were implanted in the brain of eight rats. Fifteen days later, 4.7-T MR examinations were performed to estimate T2*, T2, BVf, and T2*ΔB 0corrected in the tumor and contralateral regions. MR estimates of SO 2 were derived by combining T2, BVf, and T2*ΔB 0corrected according to a recently described quantitative BOLD approach. Scatterplots and linear regression analysis were used to identify correlation between parameters. Paired Student t tests were used to compare the tumor region with the contralateral region. Results: No significant correlations were found between T2*and any parameter in either tumor tissue or healthy tissue. T2*in the tumor and T2*in the uninvolved contralateral brain were the same (36 msec ± 4 [standard deviation] vs 36 msec ± 5, respectively), which might suggest similar oxygenation. Adding T2 information (98 msec ± 7 vs 68 msec ± 2, respectively) alone yields results that suggest apparent hypo-oxygenation of the tumor, while incorporating BVf (5.3% ± 0.6 vs 2.6% ± 0.3, respectively) alone yields results that suggest apparent hyperoxygenation. MR estimates of SO 2 obtained with a complete quantitative BOLD analysis, although not correlated with T2*values, suggest normal oxygenation (68% ± 3 vs 65% ± 4, respectively). MR estimates of SO 2 obtained in the contralateral tissue agree with previously reported values. Conclusion: Additional measurements, such as BVf, T2, and ΔB 0, are needed to obtain reliable information on oxygenation with BOLD MR imaging. The proposed quantitative BOLD approach, which includes these measurements, appears to be a promising tool with which to map tumor oxygenation. © RSNA, 2011. Source


Mirjolet C.,Center Georges Francois Leclerc | Papa A.L.,R.A.U.M. | Crehange G.,Center Georges Francois Leclerc | Raguin O.,Oncodesign | And 5 more authors.
Radiotherapy and Oncology | Year: 2013

Background and purpose One of the new challenges to improve radiotherapy is to increase the ionizing effect by using nanoparticles. The interest of titanate nanotubes (TiONts) associated with radiotherapy was evaluated in two human glioblastoma cell lines (SNB-19 and U87MG). Materials and methods Titanate nanotubes were synthetized by the hydrothermal treatment of titanium dioxide powder in a strongly basic NaOH solution. The cytotoxicity of TiONts was evaluated on SNB-19 and U87MG cell lines by cell proliferation assay. The internalization of TiONts was studied using Transmission Electron Microscopy (TEM). Finally, the effect of TiONts on cell radiosensitivity was evaluated using clonogenic assay. Cell cycle distribution was evaluated by flow cytometry after DNA labeling. DNA double-stranded breaks were evaluated using γH2AX labeling. Results Cells internalized TiONts through the possible combination of endocytosis and diffusion with no cytotoxicity. Clonogenic assays showed that cell lines incubated with TiONts were radiosensitized with a decrease in the SF2 parameter for both SNB-19 and U87MG cells. TiONts decreased DNA repair efficiency after irradiation and amplified G2/M cell-cycle arrest. Conclusion Our results indicated that further development of TiONts might provide a new useful tool for research and clinical therapy in the field of oncology. © 2013 Elsevier Ireland Ltd. All rights reserved. Source


Patent
Ipsen and Oncodesign | Date: 2015-06-23

The present invention relates to novel macrocylic compounds and compositions containing said compounds acting as kinase inhibitors, in particular as inhibitors of LRRK2 (Leucine-Rich Repeat Kinase 2). Moreover, the present invention provides processes for the preparation of the disclosed compounds, as well as methods of using them, for instance as a medicine or diagnostic agent, in particular for the treatment and/or diagnosis of diseases characterized by LRRK2 kinase activity such as neurological disorders including Parkinsons disease and Alzheimers disease.


Patent
Ipsen and Oncodesign | Date: 2014-03-14

The present invention relates to macrocyclic compounds and compositions containing said compounds acting as kinase inhibitors, in particular as inhibitors of LRRK2 kinase, for use in the diagnosis, prevention and/or treatment of LRRK2-kinase associated diseases. Moreover, the present invention provides methods of using said compounds, for instance as a medicine or diagnostic agent. Finally, the present invention also relates to new macrocyclic compounds.


Patent
Oncodesign | Date: 2012-09-28

The present invention relates to macrocylic compounds and compositions containing said compounds acting as kinase inhibitors, in particular as inhibitors of FLT3 (FMS-Related Tyrosine kinase 3). Moreover, the present invention provides processes for the preparation of the disclosed compounds, as well as methods of using them, for instance as a medicine, in particular for the treatment of cell proliferative disorders, such as cancer.

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