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168 results on '"di Tomaso E"'

1. A randomized adaptive phase II/III study of buparlisib, a pan-class I PI3K inhibitor, combined with paclitaxel for the treatment of HER2– advanced breast cancer (BELLE-4)

Author

Martín, M., Chan, A., Dirix, L., O’Shaughnessy, J., Hegg, R., Manikhas, A., Shtivelband, M., Krivorotko, P., Batista López, N., Campone, M., Ruiz Borrego, M., Khan, Q.J., Beck, J.T., Ramos Vázquez, M., Urban, P., Goteti, S., Di Tomaso, E., Massacesi, C., and Delaloge, S.

Published
2017
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3. Occurrence and Biosynthesis of Endogenous Cannabinoid Precursor,N-Arachidonoyl Phosphatidylethanolamine, in Rat Brain

Author

Cadas, H, di Tomaso, E, and Piomelli, D

Subjects
Substance Misuse, Drug Abuse (NIDA only), Neurosciences, Acyltransferases, Animals, Arachidonic Acids, Brain, Cannabinoids, Endocannabinoids, Enzymes, Lipid Metabolism, Male, Phosphatidylethanolamines, Phospholipids, Polyunsaturated Alkamides, Prodrugs, Rats, Rats, Wistar, Tissue Distribution, anandamide, N-acylethanolamines, phosphatidylethanolamine, N-acylphosphatidylethanolamine, N-acyltransferase, arachidonate, endogenous cannabinoids, Medical and Health Sciences, Psychology and Cognitive Sciences, Neurology & Neurosurgery
Abstract

It has been suggested that anandamide (N-arachidonoylethanolamine), an endogenous cannabinoid substance, may be produced through Ca2+-stimulated hydrolysis of the phosphatidylethanolamine (PE) derivative N-arachidonoyl PE. The presence of N-arachidonoyl PE in adult brain tissue and the enzyme pathways that underlie its biosynthesis are, however, still undetermined. We report here that rat brain tissue contains both anandamide (11 +/- 7 pmol/gm wet tissue) and N-arachidonoyl PE (22 +/- 16 pmol/gm), as assessed by gas chromatography/mass spectrometry. We describe a N-acyltransferase activity in brain that catalyzes the biosynthesis of N-arachidonoyl PE by transferring an arachidonate group from the sn-1 carbon of phospholipids to the amino group of PE. We also show that sn-1 arachidonoyl phospholipids are present in brain, where they constitute approximately 0.5% of total phospholipids. N-acyltransferase activity is Ca2+ dependent and is enriched in brain and testis. Within the brain, N-acyltransferase activity is highest in brainstem; intermediate in cortex, striatum, hippocampus, medulla, and cerebellum; and lowest in thalamus, hypothalamus, and olfactory bulb. Pharmacological inhibition of N-acyltransferase activity in primary cultures of cortical neurons prevents Ca2+-stimulated N-arachidonoyl PE biosynthesis. Our results demonstrate, therefore, that rat brain tissue contains the complement of enzymatic activity and lipid substrates necessary for the biosynthesis of the anandamide precursor N-arachidonoyl PE. They also suggest that biosynthesis of N-arachidonoyl PE and formation of anandamide are tightly coupled processes, which may concomitantly be stimulated by elevations in intracellular Ca2+ occurring during neural activity.

Published
1997

4. Inhibition of anandamide hydrolysis in rat brain tissue by (E)-6-(bromomethylene) tetrahydro-3-(1-naphthalenyl)-2H-pyran-2-one.

Author

Beltramo, M, di Tomaso, E, and Piomelli, D

Subjects
Brain, Cerebral Cortex, Astrocytes, Neurons, Microsomes, Liver, Animals, Rats, Rats, Wistar, Pyrones, Naphthalenes, Amidohydrolases, Arachidonic Acids, Phosphatidylcholines, Phosphatidylethanolamines, Enzyme Inhibitors, Ionophores, Endocannabinoids, Hydrolysis, Polyunsaturated Alkamides, bromoenol lactone, phospholipase A(2), amidohydrolase, anandamide, cannabinoid, Biochemistry & Molecular Biology, Biochemistry and Cell Biology, Medicinal and Biomolecular Chemistry, Evolutionary Biology
Abstract

Anandamide, an endogenous canabinoid substance, is hydrolyzed by an amidohydrolase activity present in rat brain and liver. We report that the bromoenol lactone, (E)-6-(bromomethylene) tetrahydro-3-(1-naphthalenyl)-2H-pyran-2-one (BTNP), is a potent inhibitor of this enzyme activity. BTNP prevented anandamide hydrolysis in rat brain microsomes with an IC50 of 0.8 +/- 0.3 microM. Kinetic and dialysis experiments indicated that this effect was non-competitive and irreversible. After chromatographic fractionation of the enzyme activity, BTNP was still effective, suggesting that it interacts directly with the enzyme. Anandamide hydrolysis was 12-fold greater in rat cortical neurons (1.94 +/- 0.1 pmol/min/mg protein) than in cortical astrocytes (0.16 +/- 0.01 pmol/min/mg protein) and, in either cell type, it was inhibited by BTNP (IC50 = 0.1 microM in neurons). These results suggest that BTNP may provide a useful lead for the development of novel inhibitors of anandamide hydrolysis.

Published
1997

5. Occurrence and biosynthesis of endogenous cannabinoid precursor, N-arachidonoyl phosphatidylethanolamine, in rat brain.

Author

Cadas, H, di Tomaso, E, and Piomelli, D

Subjects
Brain, Animals, Rats, Rats, Wistar, Cannabinoids, Enzymes, Acyltransferases, Arachidonic Acids, Phospholipids, Phosphatidylethanolamines, Prodrugs, Endocannabinoids, Tissue Distribution, Male, Lipid Metabolism, Polyunsaturated Alkamides, anandamide, N-acylethanolamines, phosphatidylethanolamine, N-acylphosphatidylethanolamine, N-acyltransferase, arachidonate, endogenous cannabinoids, Wistar, Neurology & Neurosurgery, Medical and Health Sciences, Psychology and Cognitive Sciences
Abstract

It has been suggested that anandamide (N-arachidonoylethanolamine), an endogenous cannabinoid substance, may be produced through Ca2+-stimulated hydrolysis of the phosphatidylethanolamine (PE) derivative N-arachidonoyl PE. The presence of N-arachidonoyl PE in adult brain tissue and the enzyme pathways that underlie its biosynthesis are, however, still undetermined. We report here that rat brain tissue contains both anandamide (11 +/- 7 pmol/gm wet tissue) and N-arachidonoyl PE (22 +/- 16 pmol/gm), as assessed by gas chromatography/mass spectrometry. We describe a N-acyltransferase activity in brain that catalyzes the biosynthesis of N-arachidonoyl PE by transferring an arachidonate group from the sn-1 carbon of phospholipids to the amino group of PE. We also show that sn-1 arachidonoyl phospholipids are present in brain, where they constitute approximately 0.5% of total phospholipids. N-acyltransferase activity is Ca2+ dependent and is enriched in brain and testis. Within the brain, N-acyltransferase activity is highest in brainstem; intermediate in cortex, striatum, hippocampus, medulla, and cerebellum; and lowest in thalamus, hypothalamus, and olfactory bulb. Pharmacological inhibition of N-acyltransferase activity in primary cultures of cortical neurons prevents Ca2+-stimulated N-arachidonoyl PE biosynthesis. Our results demonstrate, therefore, that rat brain tissue contains the complement of enzymatic activity and lipid substrates necessary for the biosynthesis of the anandamide precursor N-arachidonoyl PE. They also suggest that biosynthesis of N-arachidonoyl PE and formation of anandamide are tightly coupled processes, which may concomitantly be stimulated by elevations in intracellular Ca2+ occurring during neural activity.

Published
1997

6. Brain cannabinoids in chocolate.

Author

di Tomaso, E, Beltramo, M, and Piomelli, D

Subjects
Cells, Cultured, Animals, Rats, Cacao, Ethanolamines, Cannabinoids, Amidohydrolases, Arachidonic Acids, Endocannabinoids, Brain Chemistry, Candy, Gas Chromatography-Mass Spectrometry, Polyunsaturated Alkamides, Cells, Cultured, General Science & Technology
Published
1996

7. 1648P Deep learning identifies oncogenic genetic alterations in BRAF and NTRK in H&E whole slide images from thyroid carcinomas

Author

Williams, M., primary, Pelekanou, V., additional, Hoehne, J., additional, Zoete, J.D., additional, Schmitz, A., additional, Bal, T.A., additional, Banerji, T., additional, Ferrer, J., additional, Bernard-Gauthier, V., additional, Rudolph, M., additional, Theron, M., additional, Cabanillas, M.E., additional, Lenga, M., additional, and Di Tomaso, E., additional

Published
2022
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11. PI3K inhibitors as new cancer therapeutics: implications for clinical trial design

Author

Massacesi C, Di Tomaso E, Urban P, Germa C, Quadt C, Trandafir L, Aimone P, Fretault N, Dharan B, Tavorath R, and Hirawat S

Subjects
PI3K/AKT/mTOR pathway, biomarker, PI3K inhibitors, lcsh:Neoplasms. Tumors. Oncology. Including cancer and carcinogens, lcsh:RC254-282, clinical trial design, patient selection
Abstract

Cristian Massacesi,1 Emmanuelle Di Tomaso,2 Patrick Urban,3 Caroline Germa,4 Cornelia Quadt,5 Lucia Trandafir,1 Paola Aimone,3 Nathalie Fretault,1 Bharani Dharan,4 Ranjana Tavorath,4 Samit Hirawat4 1Novartis Oncology, Paris, France; 2Novartis Institutes for BioMedical Research Inc, Cambridge, MA, USA; 3Novartis Pharma AG, Basel, Switzerland; 4Novartis Pharmaceuticals Corporation, East Hanover, NJ, USA; 5Novartis Pharmaceuticals KK, Tokyo, Japan Abstract: The PI3K–AKT–mTOR pathway is frequently activated in cancer. PI3K inhibitors, including the pan-PI3K inhibitor buparlisib (BKM120) and the PI3Kα-selective inhibitor alpelisib (BYL719), currently in clinical development by Novartis Oncology, may therefore be effective as anticancer agents. Early clinical studies with PI3K inhibitors have demonstrated preliminary antitumor activity and acceptable safety profiles. However, a number of unanswered questions regarding PI3K inhibition in cancer remain, including: what is the best approach for different tumor types, and which biomarkers will accurately identify the patient populations most likely to benefit from specific PI3K inhibitors? This review summarizes the strategies being employed by Novartis Oncology to help maximize the benefits of clinical studies with buparlisib and alpelisib, including stratification according to PI3K pathway activation status, selective enrollment/target enrichment (where patients with PI3K pathway-activated tumors are specifically recruited), nonselective enrollment with mandatory tissue collection, and enrollment of patients who have progressed on previous targeted agents, such as mTOR inhibitors or endocrine therapy. An overview of Novartis-sponsored and Novartis-supported trials that are utilizing these approaches in a range of cancer types, including breast cancer, head and neck squamous cell carcinoma, non-small cell lung carcinoma, lymphoma, and glioblastoma multiforme, is also described. Keywords: PI3K–AKT–mTOR pathway, patient selection, biomarkers, PI3K inhibitors, clinical trial design

Published
2016

14. Pharmacodynamic and pharmacokinetic evaluation of SY-1425 (tamibarotene) in biomarker-selected acute myeloid leukemia (AML) and myelodysplastic syndrome (MDS) patients

Author

Bixby, D., primary, Vigil, C.E., additional, Jurcic, J., additional, Cook, R., additional, Sekeres, M.A., additional, Rizzieri, D., additional, Cortes, J., additional, Redner, R., additional, Steensma, D., additional, Roboz, G., additional, Moyo, T., additional, McKeown, M., additional, Waters, N., additional, Stephens, K., additional, di Tomaso, E., additional, Roth, D.A., additional, and Stein, E., additional

Published
2017
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19. Abstract S6-01: PIK3CA status in circulating tumor DNA (ctDNA) predicts efficacy of buparlisib (BUP) plus fulvestrant (FULV) in postmenopausal women with endocrine-resistant HR+/HER2– advanced breast cancer (BC): First results from the randomized, phase III BELLE-2 trial

Author

Baselga, J, primary, Im, S-A, additional, Iwata, H, additional, Clemons, M, additional, Ito, Y, additional, Awada, A, additional, Chia, S, additional, Jagiello-Gruszfeld, A, additional, Pistilli, B, additional, Tseng, L-M, additional, Hurvitz, S, additional, Masuda, N, additional, Cortés, J, additional, De Laurentiis, M, additional, Arteaga, CL, additional, Jiang, Z, additional, Jonat, W, additional, Hachemi, S, additional, Le Mouhaër, S, additional, Di Tomaso, E, additional, Urban, P, additional, Massacesi, C, additional, and Campone, M, additional

Published
2016
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21. An approach to hybrid probabilistic models

Author

Di Tomaso E and Baldwin JF.

Subjects
inference, Bayesian networks, temporal models, fuzzy partition, soft evidence
Abstract

This paper is concerned with a development of a theory on probabilistic models, and in particular Bayesian networks, when handling continuous variables. While it is possible to deal with continuous variables without discretisation, the simplest approach is to discretise them. A fuzzy partition of continuous domains will be used, which requires an inference procedure able to deal with soft evidence. Soft evidence is a type of uncertain evidence, and it is also a result of the type of discretisation used. An algorithm for inference in multiply connected networks will be proposed and exploited for filtering and abduction in dynamic, time-invariant models, when continuous variables are present.

Published
2008

24. Effective database processing for classification and regression with continuous variables

Author

Di Tomaso E and Baldwin JF.

Subjects
LEARNING BAYESIAN NETWORKS, PROBABILISTIC NETWORKS, Computer Science::Databases
Abstract

This article proposes a method for manipulating a database of instances relative to discrete and continuous variables. A fuzzy partition is used to discretize continuous domains. A reorganized form of representing a relational database is proposed. The new form of representation is called an effective database. The effective database is tested on classification and regression problems using general Bayesian networks and Naive Bayes classifiers. The structures and the parameters of the classifiers are estimated from the effective database. An algorithm for updating with soft evidence is used to test the induced models, when continuous variables are present. The experiments show that the effective database procedure produces a selection of relevant information from data, which improves in some cases the prediction accuracy of the classifiers.

Published
2007

26. Abstract P2-16-22: A dose-finding phase lb study of BEZ235 in combination with paclitaxel in patients with HER2-negative, locally advanced or metastatic breast cancer

Author

Gil-Martin, M, primary, Fumoleau, P, additional, Isambert, N, additional, Urruticoechea, A, additional, Beck, JT, additional, Csonka, D, additional, di Tomaso, E, additional, Gaur, A, additional, Roiffe, K, additional, Urban, P, additional, Vincent, G, additional, and Campone, M, additional

Published
2013
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28. Abstract OT2-3-09: Phase III randomized study of the oral pan-PI3K inhibitor BKM120 with fulvestrant in postmenopausal women with HR+/HER2– locally advanced or metastatic breast cancer resistant to aromatase inhibitor – BELLE-2

Author

Baselga, J, primary, Campone, M, additional, Cortes, J, additional, Iwata, H, additional, de Laurentiis, M, additional, Jonat, W, additional, Di Tomaso, E, additional, Hachemi, S, additional, Goteti, S, additional, Germa, C, additional, Massacesi, C, additional, and Arteaga, C, additional

Published
2012
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29. Abstract P6-11-08: A multicenter, open-label Ph IB/II study of BEZ235, an oral dual PI3K/mTOR inhibitor, in combination with paclitaxel in patients with HER2-negative, locally advanced or metastatic breast cancer

Author

Campone, M, primary, Fumoleau, P, additional, Gil-Martin, M, additional, Isambert, N, additional, Beck, JT, additional, Becerra, C, additional, Shtivelband, M, additional, Duval, V, additional, di Tomaso, E, additional, Roussou, P, additional, Urban, P, additional, and Urruticoechea, A, additional

Published
2012
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30. Abstract OT2-3-08: Phase III randomized study of the oral pan-PI3K inhibitor BKM120 with fulvestrant in postmenopausal women with HR+/HER2– locally advanced or metastatic breast cancer, treated with aromatase inhibitor, and progressed on or after mTOR inhibitor-based treatment – BELLE-3

Author

Di Leo, A, primary, Germa, C, additional, Weber, D, additional, Di Tomaso, E, additional, Dharan, B, additional, Massacesi, C, additional, and Hirawat, S, additional

Published
2012
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31. Abstract P4-08-01: PI3K/mTOR inhibition overcomes in vitro and in vivo trastuzumab resistance independent of feedback activation of pAKT

Author

O'Brien, NA, primary, McDonald, K, additional, Tong, L, additional, Von Euw, E, additional, Conklin, D, additional, Kalous, O, additional, Di Tomaso, E, additional, Schnell, C, additional, Linnartz, R, additional, Hurvitz, SA, additional, Finn, RS, additional, Hirawat, S, additional, and Slamon, DJ, additional

Published
2012
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34. P3-16-01: Safety Profile and Clinical Activity of Single-Agent BKM120, a Pan-Class I PI3K Inhibitor, for the Treatment of Patients with Metastatic Breast Carcinoma.

Author

Rodon, J, primary, Bendell, JC, additional, Abdul, Razak AR, additional, Homji, N, additional, Trandafir, L, additional, Quadt, C, additional, Graña-Suárez, B, additional, Siu, LL, additional, Di Tomaso, E, additional, Demanse, D, additional, Massacesi, C, additional, Hirawat, S, additional, Burris, III HA, additional, and Baselga, J, additional

Published
2011
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37. Oral PI3 kinase inhibitor BKM120 monotherapy in patients (pts) with advanced solid tumors: An update on safety and efficacy.

Author

Grana, B., primary, Burris, H. A., additional, Rodon Ahnert, J., additional, Abdul Razak, A. R., additional, De Jonge, M. J., additional, Eskens, F., additional, Siu, L. L., additional, Ru, Q. C., additional, Homji, N. F., additional, Demanse, D., additional, Di Tomaso, E., additional, Cosaert, J. G. C. E., additional, Quadt, C., additional, Baselga, J., additional, and Bendell, J. C., additional

Published
2011
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40. A comparative study of circulating endothelial cells (CECs) and circulating progenitor cells (CPCs) kinetics in four multidisciplinary phase II studies of antiangiogenic agents

Author

Duda, D. G., primary, Cohen, K. S., additional, Ancukiewicz, M., additional, di Tomaso, E., additional, Zhu, A. X., additional, Penson, R. T., additional, Horowitz, N. S., additional, Batchelor, T. T., additional, Willett, C. G., additional, and Jain, R. K., additional

Published
2008
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47. 2685

Author

Kirsch, D.G., primary, Santiago, P.M., additional, Haigis, K.M., additional, di Tomaso, E., additional, Takeuchi, O., additional, Korsmeyer, S.J., additional, Bronson, R.T., additional, Jain, R.K., additional, and Jacks, T., additional

Published
2006
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