Broad targeting of resistance to apoptosis in cancer

Apoptosis or programmed cell death is natural way of removing aged cells from the body. Most of the anti-cancer therapies trigger apoptosis induction and related cell death networks to eliminate malignant cells. However, in cancer, de-regulated apoptotic signaling, particularly the activation of an anti-apoptotic systems, allows cancer cells to escape this program leading to uncontrolled proliferation resulting in tumor survival, therapeutic resistance and recurrence of cancer. This resistance is a complicated phenomenon that emanates from the interactions of various molecules and signaling pathways. In this comprehensive review we discuss the various factors contributing to apoptosis resistance in cancers. The key resistance targets that are discussed include (1) Bcl-2 and Mcl-1 proteins; (2) autophagy processes; (3) necrosis and necroptosis; (4) heat shock protein signaling; (5) the proteasome pathway; (6) epigenetic mechanisms; and (7) aberrant nuclear export signaling. The shortcomings of current therapeutic modalities are highlighted and a broad spectrum strategy using approaches including (a) gossypol; (b) epigallocatechin-3-gallate; (c) UMI-77 (d) triptolide and (e) selinexor that can be used to overcome cell death resistance is presented. This review provides a roadmap for the design of successful anti-cancer strategies that overcome resistance to apoptosis for better therapeutic outcome in patients with cancer

Étude structurale par diffraction, absorption des rayons X et simulations Monte-Carlo de matériaux zéolithiques

The organic-inorganic composites with zeolite as host matrix are mostly studied to produce performing materials for non-linear optics, optoelectronics, optical/magnetic memories. The performances of these new materials are driven by the coupling between the guest and host properties, in particular, by the molecularframework, molecular-cation interactions. Actually, only few accurate crystallographic structures of such composite are available in literature, so the guest-host interactions are still little known. In this work, I'm interested in the crystallographic structures of two composites: temperature induced spin crossover Co2+(bpy)3-zeolite X and dmpNA-mordenite that have to produce the Second Harmonic Generation signal. In the case of magnetic composite, I have particularly studied the composite precursor, zeolite Na,Co-X, in the different hydration states in order to follow an insight on structural modifications induced by water molecules desorption. Because of desorder, the structural studies are difficult. Nevertheless, the complementarities of the experimental (X-ray Diffraction and Absorption) and simulations (Monte-Carlo) approaches were fruitful to obtain the accurate partially/completely hydrated and dehydrated structures. These structures clearly show the cell volume contraction and cation migrations over dehydration that where caused by the strong cobalt-framework interactions. The crystal structure of dmpNA-mordenite has been determined from high resolution synchrotron powder diffraction and showed that zeolite straight channels are completely loaded with dmpNA molecules with a moderate tilt angle relative to the channel axe which is favourable to frequency doubling signal.Les composites organiques-inorganiques avec la zéolithe comme matrice hôte sont de plus en plus étudiés dans le but de concevoir des matériaux multifonctionnels conjuguant les propriétés de la molécule organique et celle de la zéolithe (ex. : élaboration de commutateurs magnétiques/optiques, doubleurs de fréquence). Les propriétés macroscopiques recherchées (SHG, transition de spin) dépendent des interactions entre les espèces organiques invitées et la zéolithe (charpente, cations compensateurs de charge), qui sont encore mal connue, en particulier en raison de l'absence de structures cristallographiques précises. Cette thèse s'est intéressée à deux types de composites principalement : (Co2+(bpy)3-zéolithe X) réputé présenter une transition de spin en température et dmpNA-MORdénite), à propriété potentielle de génération de second harmonique. Dans l'étude du composite magnétique, nous nous sommes particulièrement penché sur l'évolution de la structure de la zéolithe précurseur Na,Co-X dans différents état d'hydratation. Des études complémentaires par diffraction des rayons X sur monocristal, EXAFS et simulations Monte-Carlo ont mis en évidence la forte interaction entre cations cobalt et charpente aluminosilicatée ainsi que la migration des cations Co2+ accompagnant l'hydratation progressive de la zéolithe Na,Co-X. L'étude structurale du composite dmpNA-mordénite par diffraction des rayons X sur poudre (synchrotron SPring-8, Japon) a montré que les canaux droits de la mordénite sont presque totalement occupés par les molécules de dmpNA, qui adoptent un empilement quasi linéaire favorable à la Génération de Seconde Harmonique

Structural study of zeolite materials by X-ray diffraction and absorption, and Monte-Carlo simulations

Les composites organiques-inorganiques avec la zéolithe comme matrice hôte sont de plus en plus étudiés dans le but de concevoir des matériaux multifonctionnels conjuguant les propriétés de la molécule organique et celle de la zéolithe (ex. : élaboration de commutateurs magnétiques/optiques, doubleurs de fréquence). Les propriétés macroscopiques recherchées (SHG, transition de spin) dépendent des interactions entre les espèces organiques invitées et la zéolithe (charpente, cations compensateurs de charge), qui sont encore mal connue, en particulier en raison de l'absence de structures cristallographiques précises. Cette thèse s'est intéressée à deux types de composites principalement : (Co2+(bpy)3-zéolithe X) réputé présenter une transition de spin en température et dmpNA-MORdénite), à propriété potentielle de génération de second harmonique. Dans l’étude du composite magnétique, nous nous sommes particulièrement penché sur l'évolution de la structure de la zéolithe précurseur Na,Co-X dans différents état d’hydratation. Des études complémentaires par diffraction des rayons X sur monocristal, EXAFS et simulations Monte-Carlo ont mis en évidence la forte interaction entre cations cobalt et charpente aluminosilicatée ainsi que la migration des cations Co2+ accompagnant l'hydratation progressive de la zéolithe Na,Co-X. L’étude structurale du composite dmpNA-mordénite par diffraction des rayons X sur poudre (synchrotron SPring-8, Japon) a montré que les canaux droits de la mordénite sont presque totalement occupés par les molécules de dmpNA, qui adoptent un empilement quasi linéaire favorable à la Génération de Seconde Harmonique.The organic-inorganic composites with zeolite as host matrix are mostly studied to produce performing materials for non-linear optics, optoelectronics, optical/magnetic memories. The performances of these new materials are driven by the coupling between the guest and host properties, in particular, by the molecularframework, molecular-cation interactions. Actually, only few accurate crystallographic structures of such composite are available in literature, so the guest-host interactions are still little known. In this work, I’m interested in the crystallographic structures of two composites: temperature induced spin crossover Co2+(bpy)3-zeolite X and dmpNA-mordenite that have to produce the Second Harmonic Generation signal. In the case of magnetic composite, I have particularly studied the composite precursor, zeolite Na,Co-X, in the different hydration states in order to follow an insight on structural modifications induced by water molecules desorption. Because of desorder, the structural studies are difficult. Nevertheless, the complementarities of the experimental (X-ray Diffraction and Absorption) and simulations (Monte-Carlo) approaches were fruitful to obtain the accurate partially/completely hydrated and dehydrated structures. These structures clearly show the cell volume contraction and cation migrations over dehydration that where caused by the strong cobalt –framework interactions. The crystal structure of dmpNA-mordenite has been determined from high resolution synchrotron powder diffraction and showed that zeolite straight channels are completely loaded with dmpNA molecules with a moderate tilt angle relative to the channel axe which is favourable to frequency doubling signal

Étude structurale par diffraction, absorption des rayons X et simulations Monte-Carlo de matériaux zéolithiques

Les composites organiques-inorganiques avec la zéolithe comme matrice hôte sont de plus en plus étudiés dans le but de concevoir des matériaux multifonctionnels conjuguant les propriétés de la molécule organique et celle de la zéolithe (ex. : élaboration de commutateurs magnétiques/optiques, doubleurs de fréquence). Les propriétés macroscopiques recherchées (SHG, transition de spin) dépendent des interactions entre les espèces organiques invitées et la zéolithe (charpente, cations compensateurs de charge), qui sont encore mal connue, en particulier en raison de l'absence de structures cristallographiques précises. Cette thèse s'est intéressée à deux types de composites principalement : (Co2+(bpy)3-zéolithe X) réputé présenter une transition de spin en température et dmpNA-MORdénite), à propriété potentielle de génération de second harmonique. Dans l étude du composite magnétique, nous nous sommes particulièrement penché sur l'évolution de la structure de la zéolithe précurseur Na,Co-X dans différents état d hydratation. Des études complémentaires par diffraction des rayons X sur monocristal, EXAFS et simulations Monte-Carlo ont mis en évidence la forte interaction entre cations cobalt et charpente aluminosilicatée ainsi que la migration des cations Co2+ accompagnant l'hydratation progressive de la zéolithe Na,Co-X. L étude structurale du composite dmpNA-mordénite par diffraction des rayons X sur poudre (synchrotron SPring-8, Japon) a montré que les canaux droits de la mordénite sont presque totalement occupés par les molécules de dmpNA, qui adoptent un empilement quasi linéaire favorable à la Génération de Seconde Harmonique.The organic-inorganic composites with zeolite as host matrix are mostly studied to produce performing materials for non-linear optics, optoelectronics, optical/magnetic memories. The performances of these new materials are driven by the coupling between the guest and host properties, in particular, by the molecularframework, molecular-cation interactions. Actually, only few accurate crystallographic structures of such composite are available in literature, so the guest-host interactions are still little known. In this work, I m interested in the crystallographic structures of two composites: temperature induced spin crossover Co2+(bpy)3-zeolite X and dmpNA-mordenite that have to produce the Second Harmonic Generation signal. In the case of magnetic composite, I have particularly studied the composite precursor, zeolite Na,Co-X, in the different hydration states in order to follow an insight on structural modifications induced by water molecules desorption. Because of desorder, the structural studies are difficult. Nevertheless, the complementarities of the experimental (X-ray Diffraction and Absorption) and simulations (Monte-Carlo) approaches were fruitful to obtain the accurate partially/completely hydrated and dehydrated structures. These structures clearly show the cell volume contraction and cation migrations over dehydration that where caused by the strong cobalt framework interactions. The crystal structure of dmpNA-mordenite has been determined from high resolution synchrotron powder diffraction and showed that zeolite straight channels are completely loaded with dmpNA molecules with a moderate tilt angle relative to the channel axe which is favourable to frequency doubling signal.NANCY1-Bib. numérique (543959902) / SudocSudocFranceF

Simultaneous sound velocity and density measurements of hcp iron up to 93 GPa and 1100 K: An experimental test of the Birch's law at high temperature

International audienceWe performed sound velocity and density measurements on polycrystalline hexagonal close-packed (hcp) iron at simultaneous high pressure and high temperature, up to 93 GPa and 1100 K, by inelastic x-ray scattering and x-ray diffraction. Our experimental results indicate that high-temperature anharmonic corrections are negligible at least up to 1100 K and that the aggregate compressional velocity VP scales linearly with density over the pressure and temperature range of the investigation (Birch's law). The new results are compared with literature studies and we discuss the extrapolation schemes commonly used in experimental mineral physics, with specific regard to extrapolations to the Earth's core condition