IRIS study: a phase II study of the steroid sulfatase inhibitor Irosustat when added to an aromatase inhibitor in ER-positive breast cancer patients

Purpose: Irosustat is a first-generation, orally active, irreversible steroid sulfatase inhibitor. We performed a multicentre, open label phase II trial of the addition of Irosustat to a first-line aromatase inhibitor (AI) in patients with advanced BC to evaluate the safety of the combination and to test the hypothesis that the addition of Irosustat to AI may further suppress estradiol levels and result in clinical benefit. Experimental design: Postmenopausal women with ER-positive locally advanced or metastatic breast cancer who had derived clinical benefit from a first-line AI and who subsequently progressed were enrolled. The first-line AI was continued and Irosustat (40 mg orally daily) added. The primary endpoint was clinical benefit rate (CBR). Secondary endpoints included safety, tolerability, and pharmacodynamic end points. Results: Twenty-seven women were recruited, four discontinued treatment without response assessment. Based on local reporting, the CBR was 18.5% (95% CI 6.3–38.1%) on an intent to treat basis, increasing to 21.7% (95% CI 7.4–43.7%) by per-protocol analysis. In those patients that achieved clinical benefit (n = 5), the median (interquartile range) duration was 9.4 months (8.1–11.3) months. The median progression-free survival time was 2.7 months (95% CI 2.5–4.6) in both the ITT and per-protocol analyses. The most frequently reported grade 3/4 toxicities were dry skin (28%), nausea (13%), fatigue (13%), diarrhoea (8%), headache (7%), anorexia (7%) and lethargy (7%). Conclusions: The addition of Irosustat to aromatase inhibitor therapy resulted in clinical benefit with an acceptable safety profile. The study met its pre-defined success criterion by both local and central radiological assessments

Controle hormonal de la croissance des tumeurs mammaires: role des androgenes

SIGLEAvailable from INIST (FR), Document Supply Service, under shelf-number : T 82576 / INIST-CNRS - Institut de l'Information Scientifique et TechniqueFRFranc

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International audienc

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International audienc

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International audienc

Radiolysis as a solution for accelerated ageing studies of electrolytes in Lithium-ion batteries

International audienceDiethyl carbonate and dimethyl carbonate are prototype examples of eco-friendly solvents used in lithium-ion batteries. Nevertheless, their degradation products affect both the battery performance and its safety. Therefore, it is of paramount importance to understand the reaction mechanisms involved in the ageing processes. Among those, redox processes are likely to play a critical role. Here we show that radiolysis is an ideal tool to generate the electrolytes degradation products. The major gases detected after irradiation (H 2 , CH 4 , C 2 H 6 , CO and CO 2) are identified and quantified. Moreover, the chemical compounds formed in the liquid phase are characterized by different mass spectrometry techniques. Reaction mechanisms are then proposed. The detected products are consistent with those of the cycling of Li-based cells. This demonstrates that radiolysis is a versatile and very helpful tool to better understand the phenomena occurring in lithium-ion batteries

Androgens and breast cancer

We have recently demonstrated that physiological levels of androgens exert direct and potent inhibitory effects on the growth of human breast cancer ZR-75-1 cells in vivo in nude mice as well as in vitro under both basal and estrogen-stimulated conditions. The inhibitory effect of androgens has also been confirmed on the growth of dimethylbenz(a)anthracene (DMBA)-induced mammary carcinoma in the rat. Such observations are in close agreement with the clinical data showing that androgens and the androgenic compound medroxyprogesterone acetate (MPA) have beneficial effects in breast cancer in women comparable to other endocrine therapies, including tamoxifen. Although the inhibitory action of androgens on cell proliferation in estrogen-induced ZR-75-1 cells results, in part, from their suppressive effect on expression of the estrogen receptor, the androgens also exert a direct inhibitory effect independent of estrogens. Androgens cause a global slowing effect on the duration of the cell cycle. These observations support clinical data showing that androgenic compounds induce an objective remission after failure of antiestrogen therapy as well as those indicating that the antiproliferative action of androgens is additive to that of antiestrogens. We have also recently demonstrated in ZR-75-1 human breast cancer cells the antagonism between androgens and estrogens on the expression of GCDFP-15 and GCDFP-24 which are two major proteins secreted in human gross cystic disease fluid. The effects of androgens and estrogens as well as those of progestins and glucocorticoids on GCDFP-15 and GCDFP-24 mRNA levels and secretion are opposite to those induced by the same steroids on cell growth in ZR-75-1 cells.info:eu-repo/semantics/publishe

Androgens and breast cancer

info:eu-repo/semantics/publishe

Role of PF 6 À in the radiolytical and electrochemical degradation of propylene carbonate solutions

International audienceh i g h l i g h t s g r a p h i c a l a b s t r a c t The presence of LiPF 6 in PC significantly affects the decomposition pathways. CO 2 production is doubled in irradiated PC/LiPF 6 1 M as compared to irradiated PC. This effect is specific of LiPF 6 and is not observed in other salts such as LiClO 4. A high reaction rate constant between the electron and PF 6 À in PC is measured. Radiolysis accelerates aging and enables the description of reaction mechanisms. a b s t r a c t The behavior under irradiation of neat propylene carbonate (PC), a co-solvent usually used in Li-ion batteries (LIB), and also of Li salt solutions is investigated. The decomposition of neat PC is studied using radiolysis in the pulse and steady state regime and is assigned to the ultrafast formation, in the reducing channel, of the radical anion PC À by electron attachment, followed by the ring cleavage, leading to CO. In the oxidative channel, the PC(eH) radical is formed, generating CO 2. The CO 2 and CO yields are both close to the ionization yield of PC. The CO 2 and CO productions in LiClO 4 , LiBF 4 and LiN(CF 3) 2 (SO 2) 2 solutions are similar as in neat PC. In contrast, in LiPF 6 /PC a strong impact on PC degradation is measured with a doubling of the CO 2 yield due to the high reactivity of the electron towards PF 6 À observed in the picosecond range. A small number of oxide phosphine molecules are detected among the various products of the irradiated solutions, suggesting that most of them, observed in carbonate mixtures used in LIBs, arise from linear rather than from cyclical molecules. The similarity between the degradation by radiolysis or electrolysis highlights the interest of radiolysis as an accelerated aging method

Ex situ solid electrolyte interphase synthesis via radiolysis of Li-ion battery anode–electrolyte system for improved coulombic efficiency

International audienceThe radiolysis of a mixed solvent electrolyte–carbon anode material is investigated for the first time. The present work demonstrates the radiolytic growth of an SEI with a chemical composition similar to that formed during electrochemical cycling, as determined by XPS. The quantity of the SEI increases with increasing irradiation dose. Degradation products formed in the liquid and gas phase are also identified as matching those formed during electrochemical cycling. TEM results support the XPS results of increasing SEI content with increasing irradiation dose. Electrochemical characterization by galvanostatic cycling of test cells indicates that the radiolysis generated SEI greatly improves first cycle efficiency of the materials assembled in half cells, and impedance spectroscopy supports the result with an increase in resistivity observed for irradiated samples. This first study opens the door to the use of irradiation tools for the artificial generation of an SEI and for producing LIB anode materials with improved performance