Low-dose hyper-radiosensitivity of progressive and regressive cells isolated from a rat colon tumour: impact of DNA repair.

International audiencePURPOSE: To ask whether highly metastatic sublines show more marked low-dose hyper-radiosensitivity (HRS) response than poorly metastatic ones. MATERIALS AND METHODS: The progressive (PRO) subline showing tumourigenicity and metastatic potential and the regressive (REG) subline showing neither tumourigenicity nor metastatic potential were both isolated from a parental rat colon tumour. Clonogenic survival, micronuclei and apoptosis, cell cycle distribution, DNA single- (SSB) and double-strand breaks (DSB) induction and repair were examined. RESULTS: HRS phenomenon was demonstrated in PRO subline. Before irradiation, PRO cells show more spontaneous damage than REG cells. After 0.1 Gy, PRO cells displayed: (i) More DNA SSB 15 min post-irradiation, (ii) more unrepaired DNA DSB processed by the non-homologous end-joining (NHEJ) and by the RAD51-dependent recombination pathways, (iii) more micronuclei, than REG cells while neither apoptosis nor p53 phosphorylation nor cell cycle arrest was observed in both sublines. CONCLUSIONS: HRS response of PRO subline may be induced by impairments in NHEJ repair that targets G(1) cells and RAD51-dependent repair that targets S-G(2)/M cells. The cellular consequences of such impairments are a failure to arrest in cell cycle, the propagation of damage through cell cycle, mitotic death but not p53-dependent apoptosis. Tumourigenic cells with high metastatic potential may preferentially show HRS response

Contribution of [64Cu]-ATSM PET in molecular imaging of tumour hypoxia compared to classical [18F]-MISO — a selected review

During the carcinogenesis process, tumour cells often have a more rapid proliferation potential than cells that participate in blood capillary formation by neoangiogenesis. As a consequence of the poorly organized vasculature of various solid tumours, a limited oxygen delivery is observed. This hypoxic mechanism frequently occurs in solid cancers and can lead to therapeutic resistance. The present selected literature review is focused on the comparison of two positron emitting radiopharmaceuticals agents, which are currently leaders in tumour hypoxia imaging by PET. {18F}-fluoromisonidazole (= FMISO) is most commonly used as an investigational PET agent with an investigational new drug exemption from the FDA, while {64Cu}-diacetyl-bis(N4-methylthiosemicarbazone) (64Cu-ATSM) has been presented as an alternative radiopharmaceutical not yet readily available. The comparison of these two radiopharmaceutical agents is particularly focused on isotope properties, radiopharmaceutical labelling process, pharmacological mechanisms, dosimetry data in patients, and clinical results in terms of image contrast. PET imaging has demonstrated a good efficacy in tumour hypoxia imaging with both FMISO and Cu-ATSM, but FMISO has presented too slow an in vivo accumulation and a weak image contrast of the hypoxia area. Despite a less favourable dosimetry, 64Cu-ATSM appears superior in terms of imaging performance, calling for industrial and clinical development of this innovative radiopharmaceutical. Nuclear Med Rev 2011; 14, 2: 90–9

Syndecan-1 regulates the biological activities of interleukin-34

IL-34 is a challenging cytokine sharing functional similarities with M-CSF through M-CSFR activation. It also plays a singular role that has recently been explained in the brain, through a binding to the receptor protein tyrosine phosphatase RPTPβ/ζ. The aim of this paper was to look for alternative binding of IL-34 on other cell types. Myeloid cells (HL-60, U-937, THP-1) were used as cells intrinsically expressing M-CSFR, and M-CSFR was expressed in TF-1 and HEK293 cells. IL-34 binding was studied by Scatchard and binding inhibition assays, using 125I-radiolabelled cytokines, and surface plasmon resonance. M-CSFR activation was analysed by Western blot after glycosaminoglycans abrasion, syndecan-1 overexpression or repression and addition of a blocking anti-syndecan antibody. M-CSF and IL-34 induced different patterns of M-CSFR phosphorylations, suggesting the existence of alternative binding for IL-34. Binding experiments and chondroitinase treatment confirmed low affinity binding to chondroitin sulphate chains on cells lacking both M-CSFR and RPTPβ/ζ. Amongst the proteoglycans with chondroitin sulphate chains, syndecan-1 was able to modulate the IL-34-induced M-CSFR signalling pathways. Interestingly, IL-34 induced the migration of syndecan-1 expressing cells. Indeed, IL-34 significantly increased the migration of THP-1 and M2a macrophages that was inhibited by addition of a blocking anti-syndecan-1 antibody. This paper provides evidence of alternative binding of IL-34 to chondroitin sulphates and syndecan-1 at the cell surface that modulates M-CSFR activation. In addition, IL-34-induced myeloid cell migration is a syndecan-1 dependent mechanism

Secteur traditionnel et développement rural en Mauritanie

Cherel Jacques. Secteur traditionnel et développement rural en Mauritanie. In: Tiers-Monde, tome 8, n°31, 1967. pp. 631-677

Les unités coopératives de production du Nord tunisien

Cherel Jacques. Les unités coopératives de production du Nord tunisien. In: Tiers-Monde, tome 5, n°18, 1964. pp. 235-254

Détection et abstraction de l'émergence dans des simulations de systèmes complexes (application à la savane de Côte d'Ivoire)

La notion d'émergence est au coeur des sciences des systèmes complexes et préoccupe philosophes et scientifiques. Elle parle de ces propriétés, états, phénomènes macroscopiques que l'on ne sait pas expliquer, déduire ou prédire à partir d'une connaissance complète de leurs constituants microscopiques. Ce travail se place dans le cadre de la conception d'outils d'aide à l'analyse de systèmes complexes en simulation. Une étude bibliographique présente un éventail des définitions et des problèmes conceptuels de l'émergence. L'émergence y est vue, entre autres, sous l'angle de la construction d'un langage descriptif d'un système à haut niveau. Les chapitres de cette thèse jalonnent le chemin de la construction d'un tel langage, en passant par la détection de l'émergence, la visualisation de simulations de systèmes complexes, et l'étude des interactions causales au langage plus élevé. Ce dernier aspect a été réalisé par une étude en simulation d'un modèle de savane calibré avec des données de la savane de Lamto en Côte d'Ivoire.The notion of emergence is at the core of complex systems science and concern philosophers and scientists. It is about those macroscopic properties, states, phenomena that we cannot explain, deduce or predict from the complete knowledge of their microscopic constituents. The context of this work is the conception of tools for the analysis of complex systems simulation. A literature review presents a panel of the definitions and conceptual problems of emergence. In particular, emergence is seen as the construction of a high level description of a complex system. The chapters of this thesis punctuate the path of constructing such a language. They talk about detecting emergence, visualising the traces of a complex system simulation, and studying the high level causal interactions. This last aspect was realised with a simulation study of a savanna model calibrated with data collected in the Lamto savanna in Côte d'Ivoire.PARIS-BIUSJ-Biologie recherche (751052107) / SudocSudocFranceF