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201 results on '"Raynaud F"'

2. 454O A phase (Ph) I/II trial of the CXCR2 antagonist AZD5069 in combination with enzalutamide (ENZA) in patients (pts) with metastatic castration resistant prostate cancer (mCRPC)

Author

Guo, C., primary, Sharp, A., additional, Vogl, U., additional, Colombo, I., additional, Stathis, A., additional, Jain, S., additional, Chandran, K., additional, Tiu, C., additional, Paschalis, A., additional, Matthews, R.E., additional, Figueiredo, I., additional, Rekowski, J., additional, Yap, C., additional, de los Dolores Fenor de la Maza, M., additional, Turner, A., additional, Badham, H.C., additional, Parmar, M., additional, Raynaud, F., additional, Alimonti, A., additional, and de Bono, J.S., additional

Published
2022
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6. Phase I trial of the poly(ADP-ribose) polymerase (PARP) inhibitor olaparib and AKT inhibitor capivasertib in patients with BRCA1/2 and non-BRCA1/2 mutant cancers

Author

Yap T, Kristeleit R, Michalarea V, Pettitt S, Lim J, Carreira S, Roda D, Miller R, Riisnaes R, Miranda S, Figueiredo I, Nava Rodrigues D, Ward S, Matthews R, Parmar M, Turner A, Tunariu N, Chopra N, Gevensleben H, Turner N, Ruddle R, Raynaud F, Decordova S, Swales K, Finneran L, Hall E, Rugman P, Lindemann J, Foxley A, Lord C, Banerji U, Plummer R, Basu B, Lopez J, Drew Y, and de Bono J

Abstract

Preclinical studies have demonstrated synergy between poly(ADP-ribose) polymerase (PARP) and phosphatidylinositol-3-kinase (PI3K)/AKT pathway inhibitors in BRCA1 and BRCA2 (BRCA1/2)-deficient and BRCA1/2-proficient tumors. We conducted an investigator-initiated phase I trial utilizing a prospective intrapatient dose-escalation design to assess two schedules of capivasertib (AKT inhibitor) with olaparib (PARP inhibitor) in 64 patients with advanced solid tumors. Dose expansions enrolled germline BRCA1/2-mutant tumors, or BRCA1/2-wildtype cancers harboring somatic DNA damage response (DDR) or PI3K/AKT pathway alterations. The combination was well-tolerated. Recommended phase 2 doses for the two schedules were: olaparib 300mg BID with either capivasertib 400mg BID 4-days-on, 3-days-off, or capivasertib 640mg BID 2-days-on, 5-days-off. Pharmacokinetics were dose-proportional. Pharmacodynamic studies confirmed pGSK3beta suppression, increased pERK and decreased BRCA1 expression. 25 (44.6%) of 56 evaluable patients achieved clinical benefit (RECIST CR/PR or stable disease =4 months), including patients with tumors harboring germline BRCA1/2-mutations and BRCA1/2-wildtype cancers with or without DDR and PI3K/AKT pathway alterations. Copyright ©2020, American Association for Cancer Research.

Published
2020

8. ALK2 inhibitors display beneficial effects in preclinical models of ACVR1 mutant diffuse intrinsic pontine glioma

Author

Carvalho, D, Taylor, KR, Olaciregui, NG, Molinari, V, Clarke, M, Mackay, A, Ruddle, R, Henley, A, Valenti, M, Hayes, A, Brandon, ADH, Eccles, SA, Raynaud, F, Boudhar, A, Monje, M, Popov, S, Moore, AS, Mora, J, Cruz, O, Vinci, M, Brennan, PE, Bullock, AN, Carcaboso, AM, and Jones, C

Subjects
Pyridines, Drug Evaluation, Preclinical, CNS cancer, Administration, Oral, Gene Expression, Antineoplastic Agents, Apoptosis, Mice, SCID, Article, Drug Administration Schedule, Target validation, Paediatric cancer, Mice, Cell Line, Tumor, Animals, Brain Stem Neoplasms, Humans, Child, Protein Kinase Inhibitors, lcsh:QH301-705.5, Cell Proliferation, Diffuse Intrinsic Pontine Glioma, Survival Analysis, Xenograft Model Antitumor Assays, High-Throughput Screening Assays, Pyrimidines, lcsh:Biology (General), Mutation, Pyrazoles, Female, Activin Receptors, Type I
Abstract

Diffuse intrinsic pontine glioma (DIPG) is a lethal childhood brainstem tumour, with a quarter of patients harbouring somatic mutations in ACVR1, encoding the serine/threonine kinase ALK2. Despite being an amenable drug target, little has been done to-date to systematically evaluate the role of ACVR1 in DIPG, nor to screen currently available inhibitors in patient-derived tumour models. Here we show the dependence of DIPG cells on the mutant receptor, and the preclinical efficacy of two distinct chemotypes of ALK2 inhibitor in vitro and in vivo. We demonstrate the pyrazolo[1,5-a]pyrimidine LDN-193189 and the pyridine LDN-214117 to be orally bioavailable and well-tolerated, with good brain penetration. Treatment of immunodeprived mice bearing orthotopic xenografts of H3.3K27M, ACVR1R206H mutant HSJD-DIPG-007 cells with 25 mg/kg LDN-193189 or LDN-214117 for 28 days extended survival compared with vehicle controls. Development of ALK2 inhibitors with improved potency, selectivity and advantageous pharmacokinetic properties may play an important role in therapy for DIPG patients., Diana Carvalho, Kathryn R. Taylor et al. show that ALK2 inhibitors induce apoptosis of ACVR1 mutant diffuse intrinsic pontine glioma cells in vitro. These compounds also increase the survival of mice carrying ACVR1 mutant brainstem xenografts, suggesting ALK2 as a potential pharmacological target against this lethal cancer.

Published
2019

10. Neural network modeling and geochemical wateranalyses to understand and forecast karst and non-karstpart of flash floods (case study on theLezriver,Southern France)

Author

Darras, T., Raynaud, F., Borrell Estupina, V., Kong-A-Siou, L., Van-Exter, S., Vayssade, B., Johannet, A., Pistre, S., IMT - MINES ALES (IMT - MINES ALES), Institut Mines-Télécom [Paris] (IMT), Hydrosciences Montpellier (HSM), Institut national des sciences de l'Univers (INSU - CNRS)-Institut de Recherche pour le Développement (IRD)-Université Montpellier 2 - Sciences et Techniques (UM2)-Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS), Karst et aquifères hétérogènes - Hydrogéologie et transferts (Karst), Institut national des sciences de l'Univers (INSU - CNRS)-Institut de Recherche pour le Développement (IRD)-Université Montpellier 2 - Sciences et Techniques (UM2)-Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS)-Institut national des sciences de l'Univers (INSU - CNRS)-Institut de Recherche pour le Développement (IRD)-Université Montpellier 2 - Sciences et Techniques (UM2)-Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS), Laboratoire de Génie de l'Environnement Industriel (LGEI), Institut Mines-Télécom [Paris] (IMT)-Institut Mines-Télécom [Paris] (IMT), Institut de Recherche pour le Développement (IRD)-Institut national des sciences de l'Univers (INSU - CNRS)-Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS), and Institut de Recherche pour le Développement (IRD)-Institut national des sciences de l'Univers (INSU - CNRS)-Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche pour le Développement (IRD)-Institut national des sciences de l'Univers (INSU - CNRS)-Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS)

Subjects
[SDU.STU.HY]Sciences of the Universe [physics]/Earth Sciences/Hydrology, ComputingMilieux_MISCELLANEOUS
Abstract

International audience

Published
2015
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12. The stoichiometry of scaffold complexes in living neurons -DLC2 functions as a dimerization engine for GKAP

Author

Moutin, Enora, Compan, Vincent, Raynaud, F., Clerte, Caroline, Bouquier, Nathalie, Labesse, Gilles, Ferguson, Matthew, Fagni, Laurent, Royer, Catherine, Perroy, Julie, Institut de Génomique Fonctionnelle (IGF), Université Montpellier 1 (UM1)-Université Montpellier 2 - Sciences et Techniques (UM2)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Centre de Biochimie Structurale [Montpellier] (CBS), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS), and Passerieux, Emilie

Subjects
Scaffold, [SDV.MHEP.PHY] Life Sciences [q-bio]/Human health and pathology/Tissues and Organs [q-bio.TO], Guanylate kinase-associated protein, [SDV.MHEP.PHY]Life Sciences [q-bio]/Human health and pathology/Tissues and Organs [q-bio.TO], Oligomerization, Scanning number and brightness, Dynein light chain, Bioluminescence resonance energy transfer
Abstract

International audience; Quantitative spatio-temporal characterization of protein interactions in living cells remains a major challenge facing modern biology. We have investigated in living neurons the spatial dependence of the stoichiometry of interactions between two core proteins of the N-methyl-D-aspartate (NMDA)-receptor-associated scaffolding complex, GKAP (also known as DLGAP1) and DLC2 (also known as DYNLL2), using a novel variation of fluorescence fluctuation microscopy called two-photon scanning number and brightness (sN&B). We found that dimerization of DLC2 was required for its interaction with GKAP, which, in turn, potentiated GKAP selfassociation. In the dendritic shaft, the DLC2-GKAP heterooligomeric complexes were composed mainly of two DLC2 and two GKAP monomers, whereas, in spines, the hetero-complexes were much larger, with an average of ,16 DLC2 and ,13 GKAP monomers. Disruption of the GKAP-DLC2 interaction strongly destabilized the oligomers, decreasing the spine-preferential localization of GKAP and inhibiting NMDA receptor activity. Hence, DLC2 serves a hub function in the control of glutamatergic transmission by ordering GKAP-containing complexes in dendritic spines. Beyond illuminating the role of DLC2-GKAP interactions in glutamatergic signaling, these data underscore the power of the sN&B approach for quantitative spatio-temporal imaging of other important protein complexes.

Published
2014

16. Corrections to pyridoimidazolones as novel potent inhibitors of v-raf murine sarcoma viral oncogene homologue B1 (BRAF) (Journal of Medicinal Chemistry (2009) 52, (2255-2256) DOI: 10.1021/jm801509w)

Author

Niculescu-Duvaz, D., Gaulon, C., Dijkstra, H. P., Niculescu-Duvaz, I., Zambon, A., Menard, D., Suijkerbuijk, B. M. J. M., Nourry, A., Davies, L., Manne, H., Friedlos, F., Ogilvie, L., Hedley, D., Whittaker, S., Kirk, R., Gill, A., Taylor, R. D., Raynaud, F. I., Moreno-Farre, J., Marais, R., and Springer, C. J.

Published
2009

17. A RasGAP peptide aptamer inhibits RasGAP-Aurora interaction and induces caspase-independent tumor cell death

Author

Pamonsinlapatham, P., Hadj-Slimane, R., Raynaud, F., Bickle, M., Corneloup, C., Barthelaix, A., Lepelletier, Y., Mercier, P., Schapira, M., Samson, J., Mathieu, A.L., Hugo, N., Moncorge, O., Mikaelian, I., Dufour, S., Garbay, C., Colas, P., Slama, Catherine, Cytokines, hématopoïèse et réponse immune (CHRI), Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), and Université Paris Descartes - Paris 5 (UPD5) - Institut National de la Santé et de la Recherche Médicale (INSERM) - Centre National de la Recherche Scientifique (CNRS)

Subjects
ComputingMilieux_MISCELLANEOUS
Abstract

International audience

Published
2009

19. MEDULLOBLASTOMA

Author

Vaidyanathan, G., primary, Gururangan, S., additional, Bigner, D., additional, Zalutsky, M., additional, Morfouace, M., additional, Shelat, A., additional, Megan, J., additional, Freeman, B. B., additional, Robinson, S., additional, Throm, S., additional, Olson, J. M., additional, Li, X.-N., additional, Guy, K. R., additional, Robinson, G., additional, Stewart, C., additional, Gajjar, A., additional, Roussel, M., additional, Sirachainan, N., additional, Pakakasama, S., additional, Anurathapan, U., additional, Hansasuta, A., additional, Dhanachai, M., additional, Khongkhatithum, C., additional, Hongeng, S., additional, Feroze, A., additional, Lee, K.-S., additional, Gholamin, S., additional, Wu, Z., additional, Lu, B., additional, Mitra, S., additional, Cheshier, S., additional, Northcott, P., additional, Lee, C., additional, Zichner, T., additional, Lichter, P., additional, Korbel, J., additional, Wechsler-Reya, R., additional, Pfister, S., additional, Project, I. P. T., additional, Li, K. K.-W., additional, Xia, T., additional, Ma, F. M. T., additional, Zhang, R., additional, Zhou, L., additional, Lau, K.-M., additional, Ng, H.-K., additional, Lafay-Cousin, L., additional, Chi, S., additional, Madden, J., additional, Smith, A., additional, Wells, E., additional, Owens, E., additional, Strother, D., additional, Foreman, N., additional, Packer, R., additional, Bouffet, E., additional, Wataya, T., additional, Peacock, J., additional, Taylor, M. D., additional, Ivanov, D., additional, Garnett, M., additional, Parker, T., additional, Alexander, C., additional, Meijer, L., additional, Grundy, R., additional, Gellert, P., additional, Ashford, M., additional, Walker, D., additional, Brent, J., additional, Cader, F. Z., additional, Ford, D., additional, Kay, A., additional, Walsh, R., additional, Solanki, G., additional, Peet, A., additional, English, M., additional, Shalaby, T., additional, Fiaschetti, G., additional, Baulande, S., additional, Gerber, N., additional, Baumgartner, M., additional, Grotzer, M., additional, Hayase, T., additional, Kawahara, Y., additional, Yagi, M., additional, Minami, T., additional, Kanai, N., additional, Yamaguchi, T., additional, Gomi, A., additional, Morimoto, A., additional, Hill, R., additional, Kuijper, S., additional, Lindsey, J., additional, Schwalbe, E., additional, Barker, K., additional, Boult, J., additional, Williamson, D., additional, Ahmad, Z., additional, Hallsworth, A., additional, Ryan, S., additional, Poon, E., additional, Ruddle, R., additional, Raynaud, F., additional, Howell, L., additional, Kwok, C., additional, Joshi, A., additional, Nicholson, S. L., additional, Crosier, S., additional, Wharton, S., additional, Robson, K., additional, Michalski, A., additional, Hargrave, D., additional, Jacques, T., additional, Pizer, B., additional, Bailey, S., additional, Swartling, F., additional, Petrie, K., additional, Weiss, W., additional, Chesler, L., additional, Clifford, S., additional, Kitanovski, L., additional, Prelog, T., additional, Kotnik, B. F., additional, Debeljak, M., additional, Grotzer, M. A., additional, Gevorgian, A., additional, Morozova, E., additional, Kazantsev, I., additional, Iukhta, T., additional, Safonova, S., additional, Kumirova, E., additional, Punanov, Y., additional, Afanasyev, B., additional, Zheludkova, O., additional, Grajkowska, W., additional, Pronicki, M., additional, Cukrowska, B., additional, Dembowska-Baginska, B., additional, Lastowska, M., additional, Murase, A., additional, Nobusawa, S., additional, Gemma, Y., additional, Yamazaki, F., additional, Masuzawa, A., additional, Uno, T., additional, Osumi, T., additional, Shioda, Y., additional, Kiyotani, C., additional, Mori, T., additional, Matsumoto, K., additional, Ogiwara, H., additional, Morota, N., additional, Hirato, J., additional, Nakazawa, A., additional, Terashima, K., additional, Fay-McClymont, T., additional, Walsh, K., additional, Mabbott, D., additional, Sturm, D., additional, Northcott, P. A., additional, Jones, D. T. W., additional, Korshunov, A., additional, Pfister, S. M., additional, Kool, M., additional, Hooper, C., additional, Hawes, S., additional, Kees, U., additional, Gottardo, N., additional, Dallas, P., additional, Siegfried, A., additional, Bertozzi, A. I., additional, Sevely, A., additional, Loukh, N., additional, Munzer, C., additional, Miquel, C., additional, Bourdeaut, F., additional, Pietsch, T., additional, Dufour, C., additional, Delisle, M. B., additional, Kawauchi, D., additional, Rehg, J., additional, Finkelstein, D., additional, Zindy, F., additional, Phoenix, T., additional, Gilbertson, R., additional, Trubicka, J., additional, Borucka-Mankiewicz, M., additional, Ciara, E., additional, Chrzanowska, K., additional, Perek-Polnik, M., additional, Abramczuk-Piekutowska, D., additional, Jurkiewicz, D., additional, Luczak, S., additional, Kowalski, P., additional, Krajewska-Walasek, M., additional, Sheila, C., additional, Lee, S., additional, Foster, C., additional, Manoranjan, B., additional, Pambit, M., additional, Berns, R., additional, Fotovati, A., additional, Venugopal, C., additional, O'Halloran, K., additional, Narendran, A., additional, Hawkins, C., additional, Ramaswamy, V., additional, Taylor, M., additional, Singhal, A., additional, Hukin, J., additional, Rassekh, R., additional, Yip, S., additional, Singh, S., additional, Duhman, C., additional, Dunn, S., additional, Chen, T., additional, Rush, S., additional, Fuji, H., additional, Ishida, Y., additional, Onoe, T., additional, Kanda, T., additional, Kase, Y., additional, Yamashita, H., additional, Murayama, S., additional, Nakasu, Y., additional, Kurimoto, T., additional, Kondo, A., additional, Sakaguchi, S., additional, Fujimura, J., additional, Saito, M., additional, Arakawa, T., additional, Arai, H., additional, Shimizu, T., additional, Jurkiewicz, E., additional, Daszkiewicz, P., additional, Drogosiewicz, M., additional, Hovestadt, V., additional, Buchhalter, I., additional, Jager, N. N., additional, Stuetz, A., additional, Johann, P., additional, Schmidt, C., additional, Ryzhova, M., additional, Landgraf, P., additional, Hasselblatt, M., additional, Schuller, U., additional, Yaspo, M.-L., additional, von Deimling, A., additional, Eils, R., additional, Modi, A., additional, Patel, M., additional, Berk, M., additional, Wang, L.-x., additional, Plautz, G., additional, Camara-Costa, H., additional, Resch, A., additional, Lalande, C., additional, Kieffer, V., additional, Poggi, G., additional, Kennedy, C., additional, Bull, K., additional, Calaminus, G., additional, Grill, J., additional, Doz, F., additional, Rutkowski, S., additional, Massimino, M., additional, Kortmann, R.-D., additional, Lannering, B., additional, Dellatolas, G., additional, Chevignard, M., additional, Solecki, D., additional, McKinnon, P., additional, Olson, J., additional, Hayden, J., additional, Ellison, D., additional, Buss, M., additional, Remke, M., additional, Lee, J., additional, Caspary, T., additional, Castellino, R., additional, Sabel, M., additional, Gustafsson, G., additional, Fleischhack, G., additional, Benesch, M., additional, Navajas, A., additional, Reddingius, R., additional, Delisle, M.-B., additional, Lafon, D., additional, Sevenet, N., additional, Pierron, G., additional, Delattre, O., additional, Ecker, J., additional, Oehme, I., additional, Mazitschek, R., additional, Lodrini, M., additional, Deubzer, H. E., additional, Kulozik, A. E., additional, Witt, O., additional, Milde, T., additional, Patmore, D., additional, Boulos, N., additional, Wright, K., additional, Boop, S., additional, Janicki, T., additional, Burzynski, S., additional, Burzynski, G., additional, Marszalek, A., additional, Triscott, J., additional, Green, M., additional, Rassekh, S. R., additional, Toyota, B., additional, Dunham, C., additional, Dunn, S. E., additional, Liu, K.-W., additional, Pei, Y., additional, Genovesi, L., additional, Ji, P., additional, Davis, M., additional, Ng, C. G., additional, Cho, Y.-J., additional, Jenkins, N., additional, Copeland, N., additional, Wainwright, B., additional, Tang, Y., additional, Schubert, S., additional, Nguyen, B., additional, Masoud, S., additional, Lee, A., additional, Willardson, M., additional, Bandopadhayay, P., additional, Bergthold, G., additional, Atwood, S., additional, Whitson, R., additional, Qi, J., additional, Beroukhim, R., additional, Tang, J., additional, Oro, A., additional, Link, B., additional, Bradner, J., additional, Vallero, S. G., additional, Bertin, D., additional, Basso, M. E., additional, Milanaccio, C., additional, Peretta, P., additional, Cama, A., additional, Mussano, A., additional, Barra, S., additional, Morana, G., additional, Morra, I., additional, Nozza, P., additional, Fagioli, F., additional, Garre, M. L., additional, Darabi, A., additional, Sanden, E., additional, Visse, E., additional, Stahl, N., additional, Siesjo, P., additional, Vaka, D., additional, Vasquez, F., additional, Weir, B., additional, Cowley, G., additional, Keller, C., additional, Hahn, W., additional, Gibbs, I. C., additional, Partap, S., additional, Yeom, K., additional, Martinez, M., additional, Vogel, H., additional, Donaldson, S. S., additional, Fisher, P., additional, Perreault, S., additional, Guerrini-Rousseau, L., additional, Pujet, S., additional, Kieffer-Renaux, V., additional, Raquin, M. A., additional, Varlet, P., additional, Longaud, A., additional, Sainte-Rose, C., additional, Valteau-Couanet, D., additional, Staal, J., additional, Lau, L. S., additional, Zhang, H., additional, Ingram, W. J., additional, Cho, Y. J., additional, Hathout, Y., additional, Brown, K., additional, Rood, B. R., additional, Handler, M., additional, Hankinson, T., additional, Kleinschmidt-Demasters, B. K., additional, Hutter, S., additional, Jones, D. T., additional, Kagawa, N., additional, Hirayama, R., additional, Kijima, N., additional, Chiba, Y., additional, Kinoshita, M., additional, Takano, K., additional, Eino, D., additional, Fukuya, S., additional, Yamamoto, F., additional, Nakanishi, K., additional, Hashimoto, N., additional, Hashii, Y., additional, Hara, J., additional, Yoshimine, T., additional, Wang, J., additional, Guo, C., additional, Yang, Q., additional, Chen, Z., additional, Filipek, I., additional, Swieszkowska, E., additional, Tarasinska, M., additional, Perek, D., additional, Kebudi, R., additional, Koc, B., additional, Gorgun, O., additional, Agaoglu, F. Y., additional, Wolff, J., additional, Darendeliler, E., additional, Kerl, K., additional, Gronych, J., additional, McGlade, J., additional, Endersby, R., additional, Hii, H., additional, Johns, T., additional, Sastry, J., additional, Murphy, D., additional, Ronghe, M., additional, Cunningham, C., additional, Cowie, F., additional, Jones, R., additional, Calisto, A., additional, Sangra, M., additional, Mathieson, C., additional, Brown, J., additional, Phuakpet, K., additional, Larouche, V., additional, Bartels, U., additional, Ishida, T., additional, Hasegawa, D., additional, Miyata, K., additional, Ochi, S., additional, Saito, A., additional, Kozaki, A., additional, Yanai, T., additional, Kawasaki, K., additional, Yamamoto, K., additional, Kawamura, A., additional, Nagashima, T., additional, Akasaka, Y., additional, Soejima, T., additional, Yoshida, M., additional, Kosaka, Y., additional, von Bueren, A., additional, Goschzik, T., additional, Kortmann, R., additional, von Hoff, K., additional, Friedrich, C., additional, Muehlen, A. z., additional, Warmuth-Metz, M., additional, Soerensen, N., additional, Deinlein, F., additional, Zwiener, I., additional, Faldum, A., additional, Kuehl, J., additional, KRAMER, K., additional, -Taskar, N. P., additional, Zanzonico, P., additional, Humm, J. L., additional, Wolden, S. L., additional, Cheung, N.-K. V., additional, Venkataraman, S., additional, Alimova, I., additional, Harris, P., additional, Birks, D., additional, Balakrishnan, I., additional, Griesinger, A., additional, Foreman, N. K., additional, Vibhakar, R., additional, Margol, A., additional, Robison, N., additional, Gnanachandran, J., additional, Hung, L., additional, Kennedy, R., additional, Vali, M., additional, Dhall, G., additional, Finlay, J., additional, Erdrich-Epstein, A., additional, Krieger, M., additional, Drissi, R., additional, Fouladi, M., additional, Gilles, F., additional, Judkins, A., additional, Sposto, R., additional, Asgharzadeh, S., additional, Peyrl, A., additional, Chocholous, M., additional, Holm, S., additional, Grillner, P., additional, Blomgren, K., additional, Azizi, A., additional, Czech, T., additional, Gustafsson, B., additional, Dieckmann, K., additional, Leiss, U., additional, Slavc, I., additional, Babelyan, S., additional, Dolgopolov, I., additional, Pimenov, R., additional, Mentkevich, G., additional, Gorelishev, S., additional, Laskov, M., additional, von Bueren, A. O., additional, Nowak, J., additional, Kortmann, R. D., additional, Mynarek, M., additional, Muller, K., additional, Gerber, N. U., additional, Ottensmeier, H., additional, Kwiecien, R., additional, Yankelevich, M., additional, Boyarshinov, V., additional, Glekov, I., additional, Ozerov, S., additional, Gorelyshev, S., additional, Popa, A., additional, Subbotina, N., additional, Martin, A. M., additional, Nirschl, C., additional, Polanczyk, M., additional, Bell, R., additional, Martinez, D., additional, Sullivan, L. M., additional, Santi, M., additional, Burger, P. C., additional, Taube, J. M., additional, Drake, C. G., additional, Pardoll, D. M., additional, Lim, M., additional, Li, L., additional, Wang, W.-G., additional, Pu, J.-X., additional, Sun, H.-D., additional, Ruggieri, R., additional, Symons, M. H., additional, Vanan, M. I., additional, Bolin, S., additional, Schumacher, S., additional, Zeid, R., additional, Yu, F., additional, Vue, N., additional, Gibson, W., additional, Paolella, B., additional, Swartling, F. J., additional, Kieran, M. W., additional, Bradner, J. E., additional, Maher, O., additional, Khatua, S., additional, Tarek, N., additional, Zaky, W., additional, Gupta, T., additional, Mohanty, S., additional, Kannan, S., additional, Jalali, R., additional, Kapitza, E., additional, Denkhaus, D., additional, Muhlen, A. z., additional, van Vuurden, D. G., additional, Garami, M., additional, Fangusaro, J., additional, Davidson, T. B., additional, da Costa, M. J. G., additional, Sterba, J., additional, Clifford, S. C., additional, Finlay, J. L., additional, Schmidt, R., additional, Felsberg, J., additional, Skladny, H., additional, Cremer, F., additional, Reifenberger, G., additional, Kunder, R., additional, Sridhar, E., additional, Moiyadi, A. A., additional, Goel, A., additional, Goel, N., additional, Shirsat, N., additional, Othman, R., additional, Storer, L., additional, Kerr, I., additional, Coyle, B., additional, Law, N., additional, Smith, M. L., additional, Greenberg, M., additional, Laughlin, S., additional, Malkin, D., additional, Liu, F., additional, Moxon-Emre, I., additional, Scantlebury, N., additional, Nasir, A., additional, Onion, D., additional, Lourdusamy, A., additional, Grabowska, A., additional, Cai, Y., additional, Bradshaw, T., additional, de Medeiros, R. S. S., additional, Beaugrand, A., additional, Soares, S., additional, Epelman, S., additional, Wang, W., additional, Sultan, M., additional, Wechsler-Reya, R. J., additional, Zapatka, M., additional, Radlwimmer, B., additional, Alderete, D., additional, Baroni, L., additional, Lubinieki, F., additional, Auad, F., additional, Gonzalez, M. L., additional, Puya, W., additional, Pacheco, P., additional, Aurtenetxe, O., additional, Gaffar, A., additional, Gros, L., additional, Cruz, O., additional, Calvo, C., additional, Shinojima, N., additional, Nakamura, H., additional, Kuratsu, J.-i., additional, Hanaford, A., additional, Eberhart, C., additional, Archer, T., additional, Tamayo, P., additional, Pomeroy, S., additional, Raabe, E., additional, De Braganca, K., additional, Gilheeney, S., additional, Khakoo, Y., additional, Kramer, K., additional, Wolden, S., additional, Dunkel, I., additional, Lulla, R. R., additional, Laskowski, J., additional, Goldman, S., additional, Gopalakrishnan, V., additional, Shih, D., additional, Wang, X., additional, Faria, C., additional, Raybaud, C., additional, Tabori, U., additional, Rutka, J., additional, Jacobs, S., additional, De Vathaire, F., additional, Diallo, I., additional, Llanas, D., additional, Verez, C., additional, Diop, F., additional, Kahlouche, A., additional, Puget, S., additional, Thompson, E., additional, Prince, E., additional, Amani, V., additional, Sin-Chan, P., additional, Lu, M., additional, Kleinman, C., additional, Spence, T., additional, Picard, D., additional, Ho, K. C., additional, Chan, J., additional, Majewski, J., additional, Jabado, N., additional, Dirks, P., additional, Huang, A., additional, Madden, J. R., additional, Donson, A. M., additional, Mirsky, D. M., additional, Dubuc, A., additional, Mack, S., additional, Gendoo, D., additional, Luu, B., additional, MacDonald, T., additional, Van Meter, T., additional, Croul, S., additional, Laureano, A., additional, Brugmann, W., additional, Denman, C., additional, Singh, H., additional, Huls, H., additional, Moyes, J., additional, Sandberg, D., additional, Silla, L., additional, Cooper, L., additional, and Lee, D., additional

Published
2014
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20. The calpain 1-alpha-actinin interaction. Resting complex between the calcium-dependent protease and its target in cytoskeleton

Author

Raynaud, F., BONNAL, C., Fernandez, E., Brémaud, Laure, Cerutti, M., LEBART, M.C., ROUSTAN, C., Ouali, A., Benyamin, Y., Unité de Génétique Moléculaire Animale (UGMA), Université de Limoges (UNILIM)-Institut National de la Recherche Agronomique (INRA), ProdInra, Archive Ouverte, Unité de Génétique Moléculaire Animale (UMR GMA), and Institut National de la Recherche Agronomique (INRA)-Université de Limoges (UNILIM)

Subjects
[SDV] Life Sciences [q-bio], [SDV]Life Sciences [q-bio]
Abstract

absent

Published
2003

21. Calpain 3 is expressed in astrocytes of rat and Microcebus brain

Author

Raynaud, F., Feane, H., Durand, M., Mestre-Francés, N., Rossel, M., Ouali, Ahmed, Benyamin, Y., Station de recherches sur la viande, Institut National de la Recherche Agronomique (INRA), and ProdInra, Migration

Subjects
[SPI.GPROC] Engineering Sciences [physics]/Chemical and Process Engineering, [SDV.IDA]Life Sciences [q-bio]/Food engineering, RAT, [SPI.GPROC]Engineering Sciences [physics]/Chemical and Process Engineering, [SDV.IDA] Life Sciences [q-bio]/Food engineering, IMMUNOLOGIE, ComputingMilieux_MISCELLANEOUS
Abstract

International audience

Published
2003

22. Operational tools to help stakeholders to protect and alert municipalities facing uncertainties and changes in karst flash floods.

Author

Estupina, V. Borrell, Raynaud, F., Bourgeois, N., Kong-A-Siou, L., Collet, L., Haziza, E., and Servat, E.

Subjects
FLOOD risk, STAKEHOLDERS, KARST, HYDROLOGIC models, FLOOD forecasting, RAINFALL
Abstract

Flash floods are often responsible for many deaths and involve many material damages. Regarding Mediterranean karst aquifers, the complexity of connections, between surface and groundwater, as well as weather non-stationarity patterns, increase difficulties in understanding the basins behaviour and thus warning and protecting people. Furthermore, given the recent changes in land use and extreme rainfall events, knowledge of the past floods is no longer sufficient to manage flood risks. Therefore the worst realistic flood that could occur should be considered. Physical and processes-based hydrological models are considered among the best ways to forecast floods under diverse conditions. However, they rarely match with the stakeholders' needs. In fact, the forecasting services, the municipalities, and the civil security have difficulties in running and interpreting data-consuming models in real-time, above all if data are uncertain or non-existent. To face these social and technical difficulties and help stakeholders, this study develops two operational tools derived from these models. These tools aim at planning real-time decisions given little, changing, and uncertain information available, which are: (i) a hydrological graphical tool (abacus) to estimate flood peak discharge from the karst past state and the forecasted but uncertain intense rainfall; (ii) a GIS-based method (MARE) to estimate the potential flooded pathways and areas, accounting for runoff and karst contributions and considering land use changes. Then, outputs of these tools are confronted to past and recent floods and municipalities observations, and the impacts of uncertainties and changes on planning decisions are discussed. The use of these tools on the recent 2014 events demonstrated their reliability and interest for stakeholders. This study was realized on French Mediterranean basins, in close collaboration with the Flood Forecasting Services (SPC Med-Ouest, SCHAPI, municipalities). [ABSTRACT FROM AUTHOR]

Published
2015
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24. HIGH GRADE GLIOMAS

Author

Leonard, A., primary, Wolff, J., additional, Sengupta, R., additional, Marassa, J., additional, Piwnica-Worms, D., additional, Rubin, J., additional, Pollack, I., additional, Jakacki, R., additional, Butterfield, L., additional, Okada, H., additional, Fangusaro, J., additional, Warren, K. E., additional, Mullins, C., additional, Jurgen, P., additional, Julia, S., additional, Friedrich, C. C., additional, Keir, S., additional, Saling, J., additional, Roskoski, M., additional, Friedman, H., additional, Bigner, D., additional, Moertel, C., additional, Olin, M., additional, Dahlheimer, T., additional, Gustafson, M., additional, Sumstad, D., additional, McKenna, D., additional, Low, W., additional, Nascene, D., additional, Dietz, A., additional, Ohlfest, J., additional, Sturm, D., additional, Witt, H., additional, Hovestadt, V., additional, Quan, D. A. K., additional, Jones, D. T. W., additional, Konermann, C., additional, Pfaff, E., additional, Korshunov, A., additional, Rizhova, M., additional, Milde, T., additional, Witt, O., additional, Zapatka, M., additional, Collins, V. P., additional, Kool, M., additional, Reifenberger, G., additional, Lichter, P., additional, Lindroth, A. M., additional, Plass, C., additional, Jabado, N., additional, Pfister, S. M., additional, Pizer, B., additional, Salehzadeh, A., additional, Brodbelt, A., additional, Mallucci, C., additional, Brassesco, M., additional, Pezuk, J., additional, Morales, A., additional, de Oliveira, J., additional, Roberto, G., additional, Umezawa, K., additional, Valera, E., additional, Rego, E., additional, Scrideli, C., additional, Tone, L., additional, Veringa, S. J. E., additional, Van Vuurden, D. G., additional, Wesseling, P., additional, Vandertop, W. P., additional, Noske, D. P., additional, Wurdinger, T., additional, Kaspers, G. J. L., additional, Hulleman, E., additional, Wright, K., additional, Broniscer, A., additional, Bendel, A., additional, Bowers, D., additional, Crawford, J., additional, Fisher, P., additional, Hassall, T., additional, Armstrong, G., additional, Baker, J., additional, Qaddoumi, I., additional, Robinson, G., additional, Wetmore, C., additional, Klimo, P., additional, Boop, F., additional, Onar-Thomas, A., additional, Ellison, D., additional, Gajjar, A., additional, Cruz, O., additional, de Torres, C., additional, Sunol, M., additional, Rodriguez, E., additional, Alonso, L., additional, Parareda, A., additional, Cardesa, T., additional, Salvador, H., additional, Celis, V., additional, Guillen, A., additional, Garcia, G., additional, Muchart, J., additional, Trampal, C., additional, Martin, M. L., additional, Rebollo, M., additional, Mora, J., additional, Piotrowski, A., additional, Kowalska, A., additional, Coyle, P., additional, Smith, S., additional, Rogers, H., additional, Macarthur, D., additional, Grundy, R., additional, Puccetti, D., additional, Salamat, S., additional, Kennedy, T., additional, Patel, N., additional, Bradley, K., additional, Casey, K., additional, Iskandar, B., additional, Nakano, Y., additional, Okada, K., additional, Osugi, Y., additional, Yamasaki, K., additional, Fujisaki, H., additional, Fukushima, H., additional, Inoue, T., additional, Matsusaka, Y., additional, Sakamoto, H., additional, Hara, J., additional, De Vleeschouwer, S., additional, Ardon, H., additional, Van Calenbergh, F., additional, Sciot, R., additional, Wilms, G., additional, Van Loon, J., additional, Goffin, J., additional, Van Gool, S., additional, Rusinak, D., additional, Knight, P., additional, Onel, K., additional, Wargowski, D., additional, Stettner, A., additional, Al-Ghafari, A., additional, Punjaruk, W., additional, Coyle, B., additional, Kerr, I., additional, Xipell, E., additional, Rodriguez, M., additional, Gonzalez-Huarriz, M., additional, Tunon, M. T., additional, Zazpe, I., additional, Tejada-Solis, S., additional, Diez-Valle, R., additional, Fueyo, J., additional, Gomez-Manzano, C., additional, Alonso, M. M., additional, Pastakia, D., additional, McCully, C., additional, Murphy, R., additional, Bacher, J., additional, Thomas, M., additional, Steffen-Smith, E., additional, Saleem, K., additional, Waldbridge, S., additional, Widemann, B., additional, Warren, K., additional, Miele, E., additional, Buttarelli, F., additional, Arcella, A., additional, Begalli, F., additional, Po, A., additional, Baldi, C., additional, Carissimo, G., additional, Antonelli, M., additional, Donofrio, V., additional, Morra, I., additional, Nozza, P., additional, Gulino, A., additional, Giangaspero, F., additional, Ferretti, E., additional, Elens, I., additional, Pauwels, F., additional, Fritzell, S., additional, Eberstal, S., additional, Sanden, E., additional, Visse, E., additional, Darabi, A., additional, Siesjo, P., additional, McDonald, P., additional, Wrogemann, J., additional, Krawitz, S., additional, Del Bigio, M., additional, Eisenstat, D., additional, Kwiecien, R., additional, Pietsch, T., additional, Faldum, A., additional, Kortmann, R.-D., additional, Warmuth-Metz, M., additional, Rutkowski, S., additional, Slavc, I., additional, Kramm, C. M., additional, Uparkar, U., additional, Geyer, R., additional, Ermoian, R., additional, Ellenbogen, R., additional, Leary, S., additional, Triscott, J., additional, Hu, K., additional, Fotovati, A., additional, Yip, S., additional, Kast, R., additional, Toyota, B., additional, Dunn, S., additional, Hegde, M., additional, Corder, A., additional, Chow, K., additional, Mukherjee, M., additional, Ashoori, A., additional, Brawley, V., additional, Heslop, H., additional, Gottschalk, S., additional, Yvon, E., additional, Ahmed, N., additional, Wong, T.-T., additional, Yang, F.-Y., additional, Lu, M., additional, Liang, H.-F., additional, Wang, H.-E., additional, Liu, R.-S., additional, Teng, M.-C., additional, Yen, C.-C., additional, Agnihotri, S., additional, Ternamian, C., additional, Jones, C., additional, Zadeh, G., additional, Rutka, J., additional, Hawkins, C., additional, Filipek, I., additional, Drogosiewicz, M., additional, Perek-Polnik, M., additional, Swieszkowska, E., additional, Baginska, B. D., additional, Jurkiewicz, E., additional, Perek, D., additional, Kuehn, A., additional, Falkenstein, F., additional, Gnekow, A., additional, Kramm, C., additional, Brooks, M. D., additional, Jackson, E., additional, Mitra, R. D., additional, Rubin, J. B., additional, Liu, X.-Y., additional, Schwartzentruber, J., additional, Fontebasso, A. M., additional, Quang, D.-A. K., additional, Albrecht, S., additional, Dong, Z., additional, Siegel, P., additional, Von Diemling, A., additional, Faury, D., additional, Tabori, U., additional, Majewski, J., additional, Lulla, R., additional, Echevarria, M., additional, Alden, T., additional, DiPatri, A., additional, Tomita, T., additional, Goldman, S., additional, Lin, T., additional, Merchant, T. E., additional, Kocak, M., additional, Panandiker, A. P., additional, Armstrong, G. T., additional, Gielen, G. H., additional, Muehlen, A. z., additional, Hubert, C., additional, Ding, Y., additional, Toledo, C., additional, Paddison, P., additional, Olson, J., additional, Nandhabalan, M., additional, Bjerke, L., additional, Bax, D., additional, Carvalho, D., additional, Bajrami, I., additional, Ashworth, A., additional, Lord, C., additional, Hargrave, D., additional, Reis, R., additional, Workman, P., additional, Little, S., additional, Popov, S., additional, Jury, A., additional, Burford, A., additional, Doey, L., additional, Al-Sarraj, S., additional, Jurgensmeier, J., additional, Chen, L., additional, Kozarewa, I., additional, Baker, S., additional, Perryman, L., additional, Box, G., additional, Raynaud, F., additional, Eccles, S., additional, Viana-Pereira, M., additional, Pereira, M., additional, Forshew, T., additional, Tatevossian, R., additional, Sheer, D., additional, Pimental, J., additional, Pires, M., additional, Sarkar, C., additional, Jha, P., additional, Patrick, I. R. P., additional, Somasundaram, K., additional, Pathak, P., additional, Sharma, M. C., additional, Suri, V., additional, Suri, A., additional, Gerges, N., additional, Haque, T., additional, Nantel, A., additional, Lee, C., additional, Chen, J., additional, Venugopal, C., additional, Singhal, A., additional, Dunham, C., additional, Kerr, J., additional, Verreault, M., additional, Wakimoto, H., additional, Jayanthan, A., additional, Narendran, A., additional, Singh, S., additional, Giraud, G., additional, Holm, S., additional, Gustavsson, B., additional, Kizyma, R., additional, Kizyma, Z., additional, Dvornyak, L., additional, Kotsay, B., additional, Epari, S., additional, Sharma, P., additional, Gurav, M., additional, Gupta, T., additional, Shetty, P., additional, Moiyadi, A., additional, Kane, S., additional, and Jalali, R., additional

Published
2012
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28. A phase I study of the nitroimidazole hypoxia marker SR4554 using 19F magnetic resonance spectroscopy

Author

Lee, C P, primary, Payne, G S, additional, Oregioni, A, additional, Ruddle, R, additional, Tan, S, additional, Raynaud, F I, additional, Eaton, D, additional, Campbell, M J, additional, Cross, K, additional, Halbert, G, additional, Tracy, M, additional, McNamara, J, additional, Seddon, B, additional, Leach, M O, additional, Workman, P, additional, and Judson, I, additional

Published
2009
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29. Association of type II cAMP-dependent protein kinase with p34cdc2 protein kinase in human fibroblasts

Author

Tournier S, Raynaud F, Pascale Gerbaud, Sm, Lohmann, Dorée M, and Evain-Brion D

Subjects
Adult, Blotting, Western, CDC2 Protein Kinase, Molecular Sequence Data, Humans, Amino Acid Sequence, Fibroblasts, Precipitin Tests, Protein Kinases, Cells, Cultured
Abstract

Previous independent studies suggested that type II cAMP-dependent protein kinase and the p34cdc2 protein kinase cell cycle regulator co-localize at centrosomes. In order to investigate whether there is an association of type II cAMP-dependent protein kinase with p34cdc2 in human fibroblasts, we used three different approaches. First, the regulatory subunits RI and RII were photoaffinity-labeled with 8-N3-[32P]cAMP, and anti-p34cdc2 immunoprecipitates were screened for the presence of either RI or RII regulatory subunits by one- or two-dimensional gel electrophoresis. Second, anti-RII alpha immunoprecipitates were screened for the presence of p34cdc2 by Western blot using three different affinity-purified antibodies recognizing different domains of human p34cdc2. Conversely, anti-p34cdc2 immunoprecipitates (three different antibodies), as well as the material retained on p13suc1-Sepharose Bio-Beads, which binds specifically p34cdc2, were screened for the presence of RII alpha. Finally, we have looked for cAMP-dependent protein kinase activity specifically inhibited by PKI in immunoprecipitates obtained from extracts treated with different anti-p34cdc2 antibodies. All these experiments gave concordant results and demonstrate that at least at G0/G1, human fibroblasts contain a complex of active type II cAMP-dependent protein kinase associated through its RII alpha subunit with p34cdc2.

Published
1991

30. A phase I trial of the selective oral cyclin-dependent kinase inhibitor seliciclib (CYC202; R-Roscovitine), administered twice daily for 7 days every 21 days

Author

Benson, C, primary, White, J, additional, Bono, J De, additional, O'Donnell, A, additional, Raynaud, F, additional, Cruickshank, C, additional, McGrath, H, additional, Walton, M, additional, Workman, P, additional, Kaye, S, additional, Cassidy, J, additional, Gianella-Borradori, A, additional, Judson, I, additional, and Twelves, C, additional

Published
2006
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32. A Phase I study of the angiogenesis inhibitor SU5416 (semaxanib) in solid tumours, incorporating dynamic contrast MR pharmacodynamic end points

Author

O'Donnell, A, primary, Padhani, A, additional, Hayes, C, additional, Kakkar, A J, additional, Leach, M, additional, Trigo, J M, additional, Scurr, M, additional, Raynaud, F, additional, Phillips, S, additional, Aherne, W, additional, Hardcastle, A, additional, Workman, P, additional, Hannah, A, additional, and Judson, I, additional

Published
2005
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36. Politique internationale

Author

Delieux, Delphine, Macaluso, Salvina, Amzile, T., Gilles, Alain, Philippart, Eric, Raynaud, F., Jaimurzina Djaimourzina, Azhar, Prusina, Ivan, Delieux, Delphine, Macaluso, Salvina, Amzile, T., Gilles, Alain, Philippart, Eric, Raynaud, F., Jaimurzina Djaimourzina, Azhar, and Prusina, Ivan

Abstract

SYL-001330 = Fascicule 1 ;SYL-001331 = Fascicule 2 ;SYL-001195 = Fascicule 3 ;SYL-001332 = Fascicule 4/5 ;SYL-001333 = Fascicule 6 ;SYL-001334 = Fascicule 7 ;SYL-001196 = Fascicule 8 ;SYL-001197 = Fascicule 9 ;SYL-001703 = Fascicule 10, Fascicule 1 :(World Politics) / E. Philippart -- Fascicule 2 :World Economy / A. Gilles, E. Philippart, F. Raynaud -- Fascicule 3 :Transnational issues / T. Amzile, D. Delieux -- Fascicule 4/5 :USA and CIS / A. Gilles, F. Raynaud -- Fascicule 6 :Europe / D. Delieux, S. Macaluso -- Fascicule 7 :Maghreb & Middle East / T. Amzile, D. Delieux -- Fascicule 8 :Asia & Pacific Basin / A. Gilles, S. Macaluso -- Fascicule 9 :Latin America / D. Delieux, S. Macaluso -- Fascicule 10 :Sub-Saharan Africa / Ajar Djaimourzina, Eric Philippart et Ivan Prusina, Fascicule 1-9 :5e édition 1995-1996/1 ;Fascicule 10 :5e édition 1998-1999/1, Syllabus strictement réservé aux étudiants suivant les cours dans le cadre du CERIS, info:eu-repo/semantics/published, 5

Published
1995

37. Politique internationale

Author

Philippart, Eric, Guilmain, Olivier, Doutreloux, Carine, Salkin, S., Amzile, T., Raynaud, F., Bouvier, Paule, Verhaagen, Alain, Philippart, Eric, Guilmain, Olivier, Doutreloux, Carine, Salkin, S., Amzile, T., Raynaud, F., Bouvier, Paule, and Verhaagen, Alain

Abstract

SYL-001154 = Fascicule 1 ;SYL-001155 = Fascicule 2 ;SYL-001156 = Fascicule 3 ;SYL-001157 = Fascicule 4 ;SYL-001158 = Fascicule 5 ;SYL-001159 = Fascicule 6 ;SYL-001160 = Fascicule 7 ;SYL-000795 = Fascicule 8 ;SYL-003486 = Fascicule 9 ;SYL-001161 = Fascicule 10, Fascicule 1 :World Politics / E. Philippart -- Fascicule 2 :World Political Economy / E. Philippart -- Fascicule 3 :USA et CIS / E. Philippart -- Fascicule 4 :Security and Strategy / E. Philippart -- Fascicule 5 :La nouvelle architecture européenne / O. Guilmain, C. Doutreloux -- Fascicule 6 :Maghreb & Middle East / E. Philippart, S. Salkin -- Fascicule 7 :Asia & Pacific Basin / E. Philippart -- Fascicule 8 :Sub-Saharan Africa / P. Bouvier, A. Verhaagen -- Fascicule 9 :Latin America / O. Guilmain -- Fascicule 10 :Sub-Saharan Africa / T. Amzile, F. Raynaud, Fascicule 1-3 et 6-8 :2e édition 1992-1993 ;Fascicule 4 :2e édition 1991-1992 ;Fascicule 9 :1re édition 1992-1993 ;Fascicule 10 :2e édition 1995-1996, Maitrise en Politique Internationale ;Fascicule 10 :syllabus strictement réservé aux étudiants suivant les cours dans le cadre du CERIS, info:eu-repo/semantics/published, 2

Published
1992

41. Selective FLT3 inhibition of FLT3-ITD+ acute myeloid leukaemia resulting in secondary D835Y mutation: a model for emerging clinical resistance patterns.

Author

Moore, A S, Faisal, A, de Castro, D Gonzalez, Bavetsias, V, Sun, C, Atrash, B, Valenti, M, de Haven Brandon, A, Avery, S, Mair, D, Mirabella, F, Swansbury, J, Pearson, A D J, Workman, P, Blagg, J, Raynaud, F I, Eccles, S A, and Linardopoulos, S

Subjects
ACUTE myeloid leukemia, GENETIC mutation, PROTEIN-tyrosine kinases, CHROMOSOME duplication, ALLELES
Abstract

Acquired resistance to selective FLT3 inhibitors is an emerging clinical problem in the treatment of FLT3-ITD+ acute myeloid leukaemia (AML). The paucity of valid pre-clinical models has restricted investigations to determine the mechanism of acquired therapeutic resistance, thereby limiting the development of effective treatments. We generated selective FLT3 inhibitor-resistant cells by treating the FLT3-ITD+ human AML cell line MOLM-13 in vitro with the FLT3-selective inhibitor MLN518, and validated the resistant phenotype in vivo and in vitro. The resistant cells, MOLM-13-RES, harboured a new D835Y tyrosine kinase domain (TKD) mutation on the FLT3-ITD+ allele. Acquired TKD mutations, including D835Y, have recently been identified in FLT3-ITD+ patients relapsing after treatment with the novel FLT3 inhibitor, AC220. Consistent with this clinical pattern of resistance, MOLM-13-RES cells displayed high relative resistance to AC220 and Sorafenib. Furthermore, treatment of MOLM-13-RES cells with AC220 lead to loss of the FLT3 wild-type allele and the duplication of the FLT3-ITD-D835Y allele. Our FLT3-Aurora kinase inhibitor, CCT137690, successfully inhibited growth of FLT3-ITD-D835Y cells in vitro and in vivo, suggesting that dual FLT3-Aurora inhibition may overcome selective FLT3 inhibitor resistance, in part due to inhibition of Aurora kinase, and may benefit patients with FLT3-mutated AML. [ABSTRACT FROM AUTHOR]

Published
2012
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42. Fit-for-purpose biomarker method validation for application in clinical trials of anticancer drugs.

Author

Cummings, J., Raynaud, F., Jones, L., Sugar, R., and Dive, C.

Subjects
*ANTINEOPLASTIC agents, *CLINICAL trials, *BIOMARKERS, *DRUG efficacy, *PHARMACODYNAMICS, *MICROBIOLOGICAL assay
Abstract

Clinical development of new anticancer drugs can be compromised by a lack of qualified biomarkers. An indispensable component to successful biomarker qualification is assay validation, which is also a regulatory requirement. In order to foster flexible yet rigorous biomarker method validation, the fit-for-purpose approach has recently been developed. This minireview focuses on many of the basic issues surrounding validation of biomarker assays utilised in clinical trials. It also provides an overview on strategies to validate each of the five categories that define the majority of biomarker assays. [ABSTRACT FROM AUTHOR]

Published
2010
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43. A phase I trial of the selective oral cyclin-dependent kinase inhibitor seliciclib (CYC202; R-Roscovitine), administered twice daily for 7 days every 21 days.

Author

Benson, C., White, J., De Bono, J., O'Donnell, A., Raynaud, F., Cruickshank, C., McGrath, H., Walton, M., Workman, P., Kaye, S., Cassidy, J., Gianella-Borradori, A., Judson, I., and Twelves, C.

Subjects
HYPOKALEMIA, XENOGRAFTS, RETINOBLASTOMA, NEUROBLASTOMA, PROTEIN kinases, CREATININE, PERFUSION, ANTINEOPLASTIC agents
Abstract

Seliciclib (CYC202; R-roscovitine) is the first selective, orally bioavailable inhibitor of cyclin-dependent kinases 1, 2, 7 and 9 to enter clinical trial. Preclinical studies showed antitumour activity in a broad range of human tumour xenografts. A phase I trial was performed with a 7-day b.i.d. p.o. schedule. Twenty-one patients (median age 62 years, range: 39-73 years) were treated with doses of 100, 200 and 800 b.i.d. Dose-limiting toxicities were seen at 800 mg b.i.d.; grade 3 fatigue, grade 3 skin rash, grade 3 hyponatraemia and grade 4 hypokalaemia. Other toxicities included reversible raised creatinine (grade 2), reversible grade 3 abnormal liver function and grade 2 emesis. An 800 mg portion was investigated further in 12 patients, three of whom had MAG3 renograms. One patient with a rapid increase in creatinine on day 3 had a reversible fall in renal perfusion, with full recovery by day 14, and no changes suggestive of renal tubular damage. Further dose escalation was precluded by hypokalaemia. Seliciclib reached peak plasma concentrations between 1 and 4 h and elimination half-life was 2-5 h. Inhibition of retinoblastoma protein phosphorylation was not demonstrated in peripheral blood mononuclear cells. No objective tumour responses were noted, but disease stabilisation was recorded in eight patients; this lasted for a total of six courses (18 weeks) in a patient with ovarian cancer. [ABSTRACT FROM AUTHOR]

Published
2007
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44. Hormonal impact of the 17a-hydroxylase/C17,20-lyase inhibitor abiraterone acetate (CB7630) in patients with prostate cancer.

Author

O'donnell, A, Judson, I, Dowsett, M, Raynaud, F, Dearnaley, D, Mason, M, Harland, S, Robbins, A, Halbert, G, and Nutley, B

Subjects
ENZYMES, PROSTATE cancer patients, ACETATES, PHYSIOLOGICAL effects of testosterone, PHARMACOKINETICS, HORMONES, THERAPEUTICS
Abstract

A series of three dose escalating studies were conducted to investigate the ability of the 17a-hydroxylase/C17,20-lyase inhibitor abiraterone acetate, to cause maximum suppression of testosterone synthesis when delivered to castrate and noncastrate males with prostate cancer. Study A was a single dose study in castrate males. Study B was a single dose study in noncastrate males and study C was a multiple dose study in noncastrate males. The drug was given orally in a once-daily dose and blood samples taken to assess pharmacokinetic (PK) parameters and hormone levels in all patients. The study drug was well tolerated with some variability in PKs. Suppression of testosterone levels to <0.14?nmol?l-1 was seen in four out of six castrate males treated with a single dose of 500?mg. At 800?mg given days 1-12 in noncastrate males, target suppression was achieved in three out of three patients, but a two- to three-fold increase of Luteinising Hormone (LH) levels in two out of three patients overcame suppression within 3 days. All patients in the multiple dose study developed an abnormal response to a short Synacthen test by day 11, although baseline cortisol levels remained normal. This is the first report of the use of a specific 17a-hydroxylase/17,20-lyase inhibitor in humans. Repeated treatment of men with intact gonadal function with abiraterone acetate at a dose of 800?mg can successfully suppress testosterone levels to the castrate range. However, this level of suppression may not be sustained in all patients due to compensatory hypersecretion of LH. The enhanced testosterone suppression achieved in castrate men merits further clinical study as a second-line hormonal treatment for prostate cancer. Adrenocortical suppression may necessitate concomitant administration of replacement glucocorticoid.British Journal of Cancer (2004) 90, 2317-2325. doi:10.1038/sj.bjc.6601879 www.bjcancer.com Published online 18 May 2004 [ABSTRACT FROM AUTHOR]

Published
2004
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47. High Precision Pressure-Induced Lineshifts Measured with a Frequency-Stabilized Diode Laser: Application to the ν2and (2ν2− ν2) Bands of NH3

Author

Raynaud, F., Lemoine, B., and Rohart, F.

Abstract

Pressure-induced lineshifts are measured by a new technique involving an infrared diode laser which is frequency-stabilized on the absorption peak of the studied line. Corresponding laser frequency shifts are discriminated by means of a reference cell filled with the same gas. The performance has been demonstrated on the ν2and (2ν2− ν2) lines of NH3. Pressure-induced lineshifts smaller than 10 kHz/Torr (i.e., 0.25 × 10−3cm−1/atm) are determined using a 10-Torr pressure range only. The sensitivity and reliability of this technique are critically discussed.

Published
1994
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48. Deficiency of cyclic AMP-dependent protein kinases in human psoriasis.

Author

Brion, D E, Raynaud, F, Plet, A, Laurent, P, Leduc, B, and Anderson, W

Abstract

To determine possible differences in the cyclic AMP-dependent protein kinases of normal and psoriatic human fibroblasts, the levels of the regulatory subunits (RI and RII, respectively) of protein kinase I and protein kinase II were quantitated by photoaffinity labeling with 8-azido[32P]cAMP. The level of RII was significantly decreased, or was undetectable, in cytosol prepared from fibroblasts from five psoriatic subjects when compared to RII levels found with normal human fibroblasts. The level of cytosolic RI was decreased in fibroblasts from four psoriatic patients and was within the normal range for one diseased patient when compared to RI levels in normal human fibroblasts. The elution profile from a DEAE-cellulose column of protein kinase activity in the soluble fraction from two psoriatic patients also showed a decrease in type I kinase activity and the complete absence of type II kinase activity. Other results indicate that the level of RI in erythrocyte membranes from psoriatic subjects is significantly decreased when compared to that of erythrocyte membranes from eight normal subjects. A significant correlation (P less than 0.001) was observed between the severity of the cutaneous manifestation of the disease and the level of RI in psoriatic erythrocyte membranes. The changes noted in the levels of RI and RII in cell types other than those thought to be specifically involved in the proliferative epidermis disorder of the disease suggest a general protein kinase deficiency.

Published
1986
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