31 results on '"Xuereb L"'
Search Results
2. A phase Ib dose allocation study of oral administration of lucitanib given in combination with fulvestrant in patients with estrogen receptor-positive and FGFR1-amplified or non-amplified metastatic breast cancer
- Author
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Campone, M., Bachelot, T., Penault-Llorca, F., Pallis, A., Agrapart, V., Pierrat, M. J., Poirot, C., Dubois, F., Xuereb, L., Bossard, C. J., Guigal-Stephan, N., Lockhart, B., and Andre, F.
- Published
- 2019
- Full Text
- View/download PDF
3. P.188 Anaesthetic management of a parturient with DAO enzyme deficiency, postural orthostatic tachycardia syndrome and joint hypermobility
- Author
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Xuereb, L. Borg, primary and Halder, S., additional
- Published
- 2022
- Full Text
- View/download PDF
4. A new molecular classification to drive precision treatment strategies in primary Sjögren's syndrome
- Author
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Agence Nationale de la Recherche (France), European Commission, Soret, P., Le Dantec, C., Desvaux, E., Foulquier, N., Chassagnol, B., Hubert, S., Jamin, C., Barturen, Guillermo, Desachy, G., Devauchelle-Pensec, V., Boudjeniba, C., Cornec, D., Saraux, A., Jousse-Joulin, S., Barbarroja, N., Rodríguez-Pintó, I., De Langhe, E., Beretta, L., Chizzolini, C., Kovács, L., Witte, T., PRECISESADS Clinical Consortium, PRECISESADS Flow Cytometry Consortium, Bettacchioli, E., Buttgereit, A., Makowska, Z., Lesche, R., Borghi, M. O., Martín, J., Courtade-Gaiani, S, Xuereb, L., Guedj, M, Moingeon, P., Alarcón-Riquelme, M. E., Laigle, L., Pers, Jacques-Olivier, Agence Nationale de la Recherche (France), European Commission, Soret, P., Le Dantec, C., Desvaux, E., Foulquier, N., Chassagnol, B., Hubert, S., Jamin, C., Barturen, Guillermo, Desachy, G., Devauchelle-Pensec, V., Boudjeniba, C., Cornec, D., Saraux, A., Jousse-Joulin, S., Barbarroja, N., Rodríguez-Pintó, I., De Langhe, E., Beretta, L., Chizzolini, C., Kovács, L., Witte, T., PRECISESADS Clinical Consortium, PRECISESADS Flow Cytometry Consortium, Bettacchioli, E., Buttgereit, A., Makowska, Z., Lesche, R., Borghi, M. O., Martín, J., Courtade-Gaiani, S, Xuereb, L., Guedj, M, Moingeon, P., Alarcón-Riquelme, M. E., Laigle, L., and Pers, Jacques-Olivier
- Abstract
There is currently no approved treatment for primary Sjögren’s syndrome, a disease thatprimarily affects adult women. The difficulty in developing effective therapies is -in part-because of the heterogeneity in the clinical manifestation and pathophysiology of the disease.Finding common molecular signatures among patient subgroups could improve our under-standing of disease etiology, and facilitate the development of targeted therapeutics. Here,we report, in a cross-sectional cohort, a molecular classification scheme for Sjögren’s syn-drome patients based on the multi-omic profiling of whole blood samples from a Europeancohort of over 300 patients, and a similar number of age and gender-matched healthyvolunteers. Using transcriptomic, genomic, epigenetic, cytokine expression andflow cyto-metry data, combined with clinical parameters, we identify four groups of patients withdistinct patterns of immune dysregulation. The biomarkers we identify can be used bymachine learning classifiers to sort future patients into subgroups, allowing the re-evaluationof response to treatments in clinical trials.
- Published
- 2021
5. Age alters peripheral vascular endothelial function without affecting coronary flow reserve in healthy volunteers
- Author
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Bouly, M, primary, Bourguignon, M.P, additional, Ley, S, additional, Xuereb, L, additional, Bernhardt, P, additional, and Tyl, B, additional
- Published
- 2020
- Full Text
- View/download PDF
6. Lucitanib for the treatment of HR+ HER2- metastatic breast cancer (MBC) patients (pts): Results from the multicohort phase II FINESSE trial
- Author
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Hui, R., primary, Pearson, A., additional, Cortes Castan, J., additional, Campbell, C., additional, Poirot, C., additional, Azim, H.A., additional, Fumagalli, D., additional, Lambertini, M., additional, Daly, F., additional, Arahmani, A., additional, Perez-Garcia, J., additional, Aftimos, P.G., additional, Bedard, P., additional, Xuereb, L., additional, Loibl, S., additional, Loi, S., additional, Pierrat, M.-J., additional, Turner, N.C., additional, André, F., additional, and Curigliano, G., additional
- Published
- 2018
- Full Text
- View/download PDF
7. Abstract P1-09-11: A phase Ib study of oral administration of lucitanib in combination with fulvestrant in patients with HR+ metastatic breast cancer (mBC)
- Author
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Campone, M, primary, Bachelot, T, additional, Penault-Llorca, F, additional, Pallis, A, additional, Agrapart, V, additional, Pierrat, M-J, additional, Poirot, C, additional, Paux, G, additional, Dubois, F, additional, Xuereb, L, additional, Robert, R, additional, and Andre, F, additional
- Published
- 2018
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- View/download PDF
8. Does Preoperative Atrial Fibrillation Increase the Incidence of Thromboembolic Complications in Patients Supported with Long-Term LVADs?
- Author
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Xuereb, L., primary, Kaur, B., additional, Akrawe, S., additional, Nemeh, H.W., additional, Borgi, J., additional, Lanfear, D.E., additional, Williams, C.T., additional, Paone, G., additional, and Morgan, J.A., additional
- Published
- 2016
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9. Drive Line Infections Are Not Associated with an Increased Incidence of Thromboembolic Complications in Patients on Continuous Flow LVAD Support
- Author
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Xuereb, L., primary, Kaur, B., additional, Akrawe, S., additional, Rashty, J., additional, Nemeh, H.W., additional, Borgi, J., additional, Tita, C., additional, Selektor, Y., additional, Velez, M., additional, Lanfear, D.E., additional, Williams, C.T., additional, Paone, G., additional, and Morgan, J.A., additional
- Published
- 2016
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- View/download PDF
10. Reoperation for Bleeding Does Not Adversely Impact Long-Term Outcomes in LVAD Recipients
- Author
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Xuereb, L., primary, Kaur, B., additional, Akrawe, S., additional, Rashty, J., additional, Nemeh, H.W., additional, Borgi, J., additional, Lanfear, D.E., additional, Williams, C.T., additional, Paone, G., additional, and Morgan, J.A., additional
- Published
- 2016
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- View/download PDF
11. 289PD - Lucitanib for the treatment of HR+ HER2- metastatic breast cancer (MBC) patients (pts): Results from the multicohort phase II FINESSE trial
- Author
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Hui, R., Pearson, A., Cortes Castan, J., Campbell, C., Poirot, C., Azim, H.A., Jr., Fumagalli, D., Lambertini, M., Daly, F., Arahmani, A., Perez-Garcia, J., Aftimos, P.G., Bedard, P., Xuereb, L., Loibl, S., Loi, S., Pierrat, M.-J., Turner, N.C., André, F., and Curigliano, G.
- Published
- 2018
- Full Text
- View/download PDF
12. Aging and Obesity Induce Distinct Gene Expression Adaptation in the Liver of C57BL/6J Mice
- Author
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Capel, F., primary, Delmotte, M.H., additional, Brun, M., additional, Lonchampt, M., additional, De Fanti, B., additional, Xuereb, L., additional, Baschet, L., additional, Rolland, G., additional, Galizzi, J.P., additional, Lockhart, B., additional, Ktorza, A., additional, and Dacquet, C., additional
- Published
- 2011
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13. Amylin in the periphery.
- Author
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Wookey, PJ, Xuereb, L, Tikellis, C, Cooper, ME, Wookey, PJ, Xuereb, L, Tikellis, C, and Cooper, ME
- Abstract
Amylin (islet amyloid polypeptide) is a peptide synthesized principally in the beta-cells of the pancreatic islets together with insulin and has actions as a hormone, growth factor, and modifier of behavior. As a hormone, amylin acts to modify gastric motility, renal resorption, and has metabolic actions. It is postulated that the principal function of amylin as a hormone is the activation of physiological processes associated with feeding. As a growth factor, amylin acts on bone cells, renal proximal tubular cells, and islet beta-cells. Amylin has important targets in the brain that mediate its actions in the modification of behavior, including thirst and satiety. In man, amylin can form islet amyloid deposits, an event linked to the reduction of b-cell mass and loss of signal-secretion coupling. Recent evidence has defined a new role for monomeric amylin as a growth factor and regulator of beta-cell mass that is postulated to be a key factor in pathophysiological processes that result in overt diabetes.
- Published
- 2003
14. Aging and Obesity Induce Distinct Gene Expression Adaptation in the Liver of C57BL/6J Mice.
- Author
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Capel, F., Delmotte, M.H., Brun, M., Lonchampt, M., De Fanti, B., Xuereb, L., Baschet, L., Rolland, G., Galizzi, J.P., Lockhart, B., Ktorza, A., and Dacquet, C.
- Published
- 2011
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15. (331) - Does Preoperative Atrial Fibrillation Increase the Incidence of Thromboembolic Complications in Patients Supported with Long-Term LVADs?
- Author
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Xuereb, L., Kaur, B., Akrawe, S., Nemeh, H.W., Borgi, J., Lanfear, D.E., Williams, C.T., Paone, G., and Morgan, J.A.
- Subjects
- *
PREOPERATIVE care , *ATRIAL fibrillation , *THROMBOEMBOLISM , *DISEASE complications , *LEFT heart ventricle , *MEDICAL equipment - Published
- 2016
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16. (678) - Reoperation for Bleeding Does Not Adversely Impact Long-Term Outcomes in LVAD Recipients.
- Author
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Xuereb, L., Kaur, B., Akrawe, S., Rashty, J., Nemeh, H.W., Borgi, J., Lanfear, D.E., Williams, C.T., Paone, G., and Morgan, J.A.
- Subjects
- *
REOPERATION , *HEMORRHAGE , *LEFT heart ventricle , *MEDICAL equipment , *HEART transplant recipients - Published
- 2016
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17. (669) - Drive Line Infections Are Not Associated with an Increased Incidence of Thromboembolic Complications in Patients on Continuous Flow LVAD Support.
- Author
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Xuereb, L., Kaur, B., Akrawe, S., Rashty, J., Nemeh, H.W., Borgi, J., Tita, C., Selektor, Y., Velez, M., Lanfear, D.E., Williams, C.T., Paone, G., and Morgan, J.A.
- Subjects
- *
HEART assist devices , *THROMBOEMBOLISM , *LEFT heart ventricle , *CLINICAL trials , *MEDICAL care - Published
- 2016
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- View/download PDF
18. Industrializing AI-powered drug discovery: lessons learned from the Patrimony computing platform.
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Guedj M, Swindle J, Hamon A, Hubert S, Desvaux E, Laplume J, Xuereb L, Lefebvre C, Haudry Y, Gabarroca C, Aussy A, Laigle L, Dupin-Roger I, and Moingeon P
- Subjects
- Humans, Precision Medicine, Artificial Intelligence, Drug Discovery
- Abstract
Introduction: As a mid-size international pharmaceutical company, we initiated 4 years ago the launch of a dedicated high-throughput computing platform supporting drug discovery. The platform named ' Patrimony' was built up on the initial predicate to capitalize on our proprietary data while leveraging public data sources in order to foster a Computational Precision Medicine approach with the power of artificial intelligence., Areas Covered: Specifically, Patrimony is designed to identify novel therapeutic target candidates. With several successful use cases in immuno-inflammatory diseases, and current ongoing extension to applications to oncology and neurology, we document how this industrial computational platform has had a transformational impact on our R&D, making it more competitive, as well time and cost effective through a model-based educated selection of therapeutic targets and drug candidates., Expert Opinion: We report our achievements, but also our challenges in implementing data access and governance processes, building up hardware and user interfaces, and acculturing scientists to use predictive models to inform decisions.
- Published
- 2022
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19. Aging increases circulating BH 2 without modifying BH 4 levels and impairs peripheral vascular function in healthy adults.
- Author
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Bouly M, Bourguignon MP, Roesch S, Rigouin P, Gosgnach W, Bossard E, Royere E, Diguet N, Sansilvestri-Morel P, Bonnin A, Xuereb L, Berson P, Komajda M, Bernhardt P, and Tyl B
- Subjects
- Adolescent, Adult, Aged, Animals, Biopterins blood, Blood Platelets metabolism, Blood Vessels physiology, Endothelium, Vascular physiology, Female, Humans, Male, Middle Aged, Rats, Inbred SHR, Rats, Inbred WKY, Rats, Zucker, Young Adult, Rats, Aging physiology, Biopterins analogs & derivatives, Endothelium, Vascular physiopathology
- Abstract
Little is known about the mechanisms of aging on vascular beds and its relationship with tetra and di-hydrobiopterin (BH
4 and BH2 ) levels. This observational clinical study analyzed the impact of aging on plasma and platelet biopterins, cutaneous blood flow (CBF), and coronary flow reserve (CFR) in healthy adults. The study enrolled healthy adults in 3 age groups: 18-30, 50-59, and 60-70 years (n = 25/group). Biopterins were assessed by LC-MS/MS using newly defined pre-analytical conditions limiting BH4 oxidation and improving long-term stability. CBF was measured by Laser Speckle Contrast Imaging coupled with acetylcholine-iontophoresis and CFR by adenosine stress cardiac magnetic resonance. In healthy adults, aging (60-70 years vs 18-30 years) significantly increased platelet BH2 (+75%, P = 0.033) and BH2 + BH4 (+31%, P = 0.033), and to a lesser extent plasma BH2 (+29%, P = 0.009) without affecting BH4 and BH4 /BH2 . Simultaneously, CBF was decreased (-23%, P = 0.004) but not CFR, CBF being inversely correlated with platelet BH2 (r = -0.42, P = 0.001) and BH2 + BH4 (r = -0.41, P = 0.002). The proportion of adults with abnormal platelet BH2 increased with age (+28% in 60-70y). These abnormal BH2 levels were significantly associated with reduced CBF and CFR (-16%, P = 0.03 and -26%, P = 0.02). In conclusion, our study showed that age-related peripheral endothelial dysfunction was associated with an increase in circulating BH2 without decreasing BH4 , the effect being more marked in platelets, the most relevant blood compartment to assess biopterin bioavailability. Peripheral but not coronary vascular function is progressively impaired with aging in healthy adults. All these findings support biopterins as therapeutic targets to improve vascular function., (Copyright © 2021 Elsevier Inc. All rights reserved.)- Published
- 2021
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20. A new molecular classification to drive precision treatment strategies in primary Sjögren's syndrome.
- Author
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Soret P, Le Dantec C, Desvaux E, Foulquier N, Chassagnol B, Hubert S, Jamin C, Barturen G, Desachy G, Devauchelle-Pensec V, Boudjeniba C, Cornec D, Saraux A, Jousse-Joulin S, Barbarroja N, Rodríguez-Pintó I, De Langhe E, Beretta L, Chizzolini C, Kovács L, Witte T, Bettacchioli E, Buttgereit A, Makowska Z, Lesche R, Borghi MO, Martin J, Courtade-Gaiani S, Xuereb L, Guedj M, Moingeon P, Alarcón-Riquelme ME, Laigle L, and Pers JO
- Subjects
- Adult, Autoantibodies blood, Biomarkers blood, Chemokines analysis, Chemokines genetics, Chemokines metabolism, Cohort Studies, Computational Biology, Computer Simulation, Cross-Sectional Studies, Cytokines analysis, Cytokines genetics, Databases, Genetic, Databases, Protein, Female, Flow Cytometry, Genome-Wide Association Study, Humans, Inflammation genetics, Inflammation immunology, Inflammation metabolism, Interferons genetics, Male, Middle Aged, Multigene Family, Polymorphism, Single Nucleotide, Proteome genetics, RNA-Seq, Sjogren's Syndrome blood, Sjogren's Syndrome genetics, Sjogren's Syndrome physiopathology, Cytokines blood, DNA Methylation genetics, Interferons blood, Proteome metabolism, Sjogren's Syndrome immunology, Transcriptome genetics
- Abstract
There is currently no approved treatment for primary Sjögren's syndrome, a disease that primarily affects adult women. The difficulty in developing effective therapies is -in part- because of the heterogeneity in the clinical manifestation and pathophysiology of the disease. Finding common molecular signatures among patient subgroups could improve our understanding of disease etiology, and facilitate the development of targeted therapeutics. Here, we report, in a cross-sectional cohort, a molecular classification scheme for Sjögren's syndrome patients based on the multi-omic profiling of whole blood samples from a European cohort of over 300 patients, and a similar number of age and gender-matched healthy volunteers. Using transcriptomic, genomic, epigenetic, cytokine expression and flow cytometry data, combined with clinical parameters, we identify four groups of patients with distinct patterns of immune dysregulation. The biomarkers we identify can be used by machine learning classifiers to sort future patients into subgroups, allowing the re-evaluation of response to treatments in clinical trials.
- Published
- 2021
- Full Text
- View/download PDF
21. Shallow Whole-Genome Sequencing from Plasma Identifies FGFR1 Amplified Breast Cancers and Predicts Overall Survival.
- Author
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Bourrier C, Pierga JY, Xuereb L, Salaun H, Proudhon C, Speicher MR, Belic J, Heitzer E, Lockhart BP, and Guigal-Stephan N
- Abstract
Background: Focal amplification of fibroblast growth factor receptor 1 ( FGFR1 ) defines a subgroup of breast cancers with poor prognosis and high risk of recurrence. We sought to demonstrate the potential of circulating cell-free DNA (cfDNA) analysis to evaluate FGFR1 copy numbers from a cohort of 100 metastatic breast cancer (mBC) patients. Methods: Formalin-fixed paraffin-embedded (FFPE) tissue samples were screened for FGFR1 amplification by FISH, and positive cases were confirmed with a microarray platform (Oncoscan
TM ). Subsequently, cfDNA was evaluated by two approaches, i.e., mFAST-SeqS and shallow whole-genome sequencing (sWGS), to estimate the circulating tumor DNA (ctDNA) allele fraction (AF) and to evaluate the FGFR1 status. Results: Tissue-based analyses identified FGFR1 amplifications in 20/100 tumors. All cases with a ctDNA AF above 3% ( n = 12) showed concordance for FGFR1 status between tissue and cfDNA. In one case, we were able to detect a high-level FGFR1 amplification, although the ctDNA AF was below 1%. Furthermore, high levels of ctDNA indicated an association with unfavorable prognosis based on overall survival. Conclusions: Screening for FGFR1 amplification in ctDNA might represent a viable strategy to identify patients eligible for treatment by FGFR inhibition, and mBC ctDNA levels might be used for the evaluation of prognosis in clinical drug trials.- Published
- 2020
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22. Lucitanib for the Treatment of HR + /HER2 - Metastatic Breast Cancer: Results from the Multicohort Phase II FINESSE Study.
- Author
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Hui R, Pearson A, Cortes J, Campbell C, Poirot C, Azim HA Jr, Fumagalli D, Lambertini M, Daly F, Arahmani A, Perez-Garcia J, Aftimos P, Bedard PL, Xuereb L, Scheepers ED, Vicente M, Goulioti T, Loibl S, Loi S, Pierrat MJ, Turner NC, Andre F, and Curigliano G
- Subjects
- Adult, Aged, Biomarkers, Tumor metabolism, Breast Neoplasms genetics, Breast Neoplasms metabolism, Breast Neoplasms pathology, Female, Gene Amplification, Humans, Middle Aged, Molecular Targeted Therapy, Neoplasm Metastasis, Patient Safety, Protein Kinase Inhibitors therapeutic use, Receptor, Fibroblast Growth Factor, Type 1 antagonists & inhibitors, Receptor, Fibroblast Growth Factor, Type 1 genetics, Treatment Outcome, Biomarkers, Tumor genetics, Breast Neoplasms drug therapy, Estrogen Receptor alpha metabolism, Naphthalenes therapeutic use, Quinolines therapeutic use, Receptor, ErbB-2 metabolism, Receptors, Progesterone metabolism
- Abstract
Purpose: The FGFR1 gene is amplified in 14% of patients with HR
+ /HER2- breast cancer. Efficacy and safety of lucitanib, an inhibitor of VEGFR1-3, FGFR1-3, and PDGFRα/β, were assessed., Patients and Methods: Patients with HR+ /HER2- metastatic breast cancer (MBC) received oral lucitanib in three centrally confirmed cohorts: (i) FGFR1 amplified, (ii) FGFR1 nonamplified, 11q13 amplified, and (iii) FGFR1 and 11q13 nonamplified. Key inclusion criteria included Eastern Cooperative Oncology Group Performance Status ≤2, ≥1 line of anticancer therapy, but ≤2 lines of chemotherapy. Primary endpoint was overall response rates (ORR) by RECIST1.1. Simon's two-stage design was used: If ≥2 patients responded among 21 patients, 20 additional patients could be enrolled in each cohort. FGFR1 copy-number variation (CNV) was determined by FISH and droplet digital PCR, whereas FGFR1 expression was determined by IHC., Results: Seventy-six patients (32/18/26 in cohorts 1/2/3) from nine countries were enrolled. The prespecified primary endpoint was met in cohort 1 with ORR of 19% [95% confidence interval (CI), 9%-35%], but not in cohorts 2 and 3 with ORR of 0% (95% CI, 0%-18%) and 15% (95% CI, 6%-34%), respectively. Frequent adverse events included hypertension (87%), hypothyroidism (45%), nausea (33%), and proteinuria (32%). Exploratory biomarker analyses suggested higher ORR in patients with high FGFR1 amplification (≥4 CNV) than those without high amplification (22% vs. 9%). ORR in patients with FGFR1-high tumors (IHC, H-score ≥50) was 25% versus 8% in FGFR1-low cancers., Conclusions: Lucitanib had modest antitumor activity and significant hypertension-related toxicity in patients with HR+ /HER2- MBC. Although based on small sample sizes, exploratory biomarker analyses suggested that patients with high FGFR1 amplification or expression might derive greater benefit., (©2019 American Association for Cancer Research.)- Published
- 2020
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23. Impact of Preoperative Atrial Fibrillation on Postoperative Thromboembolic Events After Left Ventricular Assist Device Implantation.
- Author
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Xuereb L, Go PH, Kaur B, Akrawe S, Nemeh HW, Borgi J, Williams CT, Paone G, and Morgan JA
- Subjects
- Adult, Aged, Anticoagulants administration & dosage, Anticoagulants therapeutic use, Atrial Appendage surgery, Disease Susceptibility, Equipment Failure, Female, Heart Failure complications, Heart Failure surgery, Humans, Incidence, Intensive Care Units statistics & numerical data, Kaplan-Meier Estimate, Length of Stay statistics & numerical data, Male, Middle Aged, Proportional Hazards Models, Stroke epidemiology, Stroke etiology, Thromboembolism epidemiology, Thrombophilia drug therapy, Thrombophilia etiology, Treatment Outcome, Unnecessary Procedures, Atrial Fibrillation complications, Heart-Assist Devices adverse effects, Thromboembolism etiology
- Abstract
Background: The incidence of atrial fibrillation (AF) among patients undergoing left ventricular assist device (LVAD) implantation is high. However, the impact of AF on clinical outcomes has not been clarified. We reviewed our 9-year experience of continuous flow (CF) LVADs to determine the impact of preoperative AF on stroke, device thrombosis, and survival., Methods: Between March 2006 and May 2015, 231 patients underwent implantation of 240 CF LVADs, 127 (52.9%) as bridge to transplantation and 113 (47.1%) as destination therapy. Effect of AF on postoperative outcomes was assessed by using Kaplan-Meier survival and Cox proportional hazard regression., Results: There were 78 patients (32.5%) with preoperative AF with a mean age of 55.7 ± 11.4 years. A similar incidence of stroke was found in patients with and without AF, 12.8% versus 16.0%, respectively (p = 0.803). Survival was similar, with 1-, 6-, 12-, and 24-month survivals of 96.2%, 91.7%, 84.5%, and 69.2%, respectively, for AF patients, versus 93.1%, 85.0%, 79.4%, and 74.1%, respectively, for non-AF patients (p = 0.424). Preoperative AF was not a significant independent predictor of survival with the use of Cox proportional hazard regression (hazard ratio 1.08, 95% confidence interval: 0.66 to 1.76)., Conclusions: Preoperative AF was associated with a similar incidence of postoperative stroke, device thrombosis, and survival. On the basis of these data, it seems unnecessary to perform a left atrial appendage ligation or to alter postoperative anticoagulation in patients with AF undergoing LVAD implantation., (Copyright © 2016 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.)
- Published
- 2016
- Full Text
- View/download PDF
24. Outcomes on Continuous Flow Left Ventricular Assist Devices: A Single Institutional 9-Year Experience.
- Author
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Morgan JA, Go PH, Xuereb L, Kaur B, Akrawe S, Nemeh HW, Borgi J, Lanfear DE, Williams CT, and Paone G
- Subjects
- Adult, Databases, Factual, Echocardiography, Doppler, Female, Follow-Up Studies, Heart Failure diagnosis, Hemodynamics physiology, Humans, Kaplan-Meier Estimate, Length of Stay, Male, Middle Aged, Monitoring, Physiologic methods, Multivariate Analysis, Operative Time, Predictive Value of Tests, Proportional Hazards Models, Prosthesis Failure, Retrospective Studies, Risk Assessment, Severity of Illness Index, Statistics, Nonparametric, Survival Rate, Treatment Outcome, Heart Failure mortality, Heart Failure surgery, Heart-Assist Devices statistics & numerical data, Prosthesis Design
- Abstract
Background: Continuous-flow left ventricular assist devices (LVADs) have become the standard of care for patients with advanced heart failure. The goal of this study was to review our 9-year institutional experience., Methods: From March 2006 through May 2015, 231 patients underwent implantation of 240 CF LVADs, HeartMate II LVAD (Thoratec Corp., Pleasanton, CA; n = 205) or HVAD (HeartWare Inc., Framingham, MA; n = 35). Of these, 127 devices (52.9%) were implanted as bridge to transplantation (BTT) and 113 (47.1%) as destination therapy (DT)., Results: Mean age was 51.2 ± 11.9 years for BTT patients and 58.2 ± 11.4 years for DT patients (p < 0.001). There was a higher incidence of preoperative diabetes, renal insufficiency, peripheral vascular disease, and previous cardiac operation in DT patients (p < 0.05). Survival was higher for BTT patients, with 1-, 6-, 12-, and 24-month survivals of 91.0%, 90.0%, 88.5%, and 72.1%, respectively, versus 85.3%, 81.1%, 75.6%, and 59.0%, respectively, for DT patients (p = 0.038). Gastrointestinal bleeding was the most common complication (29.6%), followed by right ventricular failure (22.5%) and stroke (15.0%), with a similar incidence for BTT and DT patients. Preoperative liver biopsy (hazard ratio [HR] 2.27, p = 0.036), mechanical support (HR 1.82, p = 0.025), aspartate transaminase (HR 1.07, p = 0.001), and alanine aminotransferase (HR 0.95, p = 0.024) were severe independent predictors of survival in multivariate analysis., Conclusions: These data indicate excellent survival for BTT and DT patients on long-term LVAD support. However, for LVAD therapy to become a plausible alternative to heart transplantation, we need to further decrease the incidence of postoperative complications., (Copyright © 2016 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.)
- Published
- 2016
- Full Text
- View/download PDF
25. Should Patients with Hepatic Fibrosis Undergo LVAD Implantation: A Comparative Analysis.
- Author
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Xuereb L, Go PH, Kaur B, Akrawe S, Borgi J, Paone G, and Morgan JA
- Subjects
- Adult, Aged, Humans, Male, Middle Aged, Multivariate Analysis, Heart-Assist Devices, Liver Cirrhosis mortality
- Abstract
The purpose of our study was to evaluate outcomes in patients with hepatic fibrosis at the time of LVAD implantation. There were five (2.1%) patients with preoperative hepatic fibrosis with a mean age of 51.2 ± 16.8 years. Survival at 180 days was significantly reduced in patients with hepatic fibrosis, 40.0% vs. 88.0%; p = 0.001. Hepatic fibrosis was a significant independent predictor of mortality in multivariate analysis (hazard ratio [HR] 2.27, p = 0.036).
- Published
- 2016
- Full Text
- View/download PDF
26. Inferring speaker attributes in adductor spasmodic dysphonia: ratings from unfamiliar listeners.
- Author
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Isetti D, Xuereb L, and Eadie TL
- Subjects
- Adult, Aged, Communication Disorders diagnosis, Communication Disorders psychology, Communication Disorders therapy, Crying psychology, Dysphonia psychology, Female, Humans, Male, Middle Aged, Quality of Life psychology, Reproducibility of Results, Self Concept, Severity of Illness Index, Social Behavior, Speech Production Measurement standards, Dysphonia diagnosis, Dysphonia therapy, Speech Intelligibility, Speech Production Measurement methods, Speech-Language Pathology methods, Voice Quality
- Abstract
Purpose: To determine whether unfamiliar listeners' perceptions of speakers with adductor spasmodic dysphonia (ADSD) differ from control speakers on the parameters of relative age, confidence, tearfulness, and vocal effort and are related to speaker-rated vocal effort or voice-specific quality of life., Method: Twenty speakers with ADSD (including 6 speakers with ADSD plus tremor) and 20 age- and sex-matched controls provided speech recordings, completed a voice-specific quality-of-life instrument (Voice Handicap Index; Jacobson et al., 1997), and rated their own vocal effort. Twenty listeners evaluated speech samples for relative age, confidence, tearfulness, and vocal effort using rating scales., Results: Listeners judged speakers with ADSD as sounding significantly older, less confident, more tearful, and more effortful than control speakers (p < .01). Increased vocal effort was strongly associated with decreased speaker confidence (rs = .88-.89) and sounding more tearful (rs = .83-.85). Self-rated speaker effort was moderately related (rs = .45-.52) to listener impressions. Listeners' perceptions of confidence and tearfulness were also moderately associated with higher Voice Handicap Index scores (rs = .65-.70)., Conclusion: Unfamiliar listeners judge speakers with ADSD more negatively than control speakers, with judgments extending beyond typical clinical measures. The results have implications for counseling and understanding the psychosocial effects of ADSD.
- Published
- 2014
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27. 2P2I HUNTER: a tool for filtering orthosteric protein-protein interaction modulators via a dedicated support vector machine.
- Author
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Hamon V, Bourgeas R, Ducrot P, Theret I, Xuereb L, Basse MJ, Brunel JM, Combes S, Morelli X, and Roche P
- Subjects
- Small Molecule Libraries, Databases, Chemical, Protein Interaction Mapping methods, Support Vector Machine
- Abstract
Over the last 10 years, protein-protein interactions (PPIs) have shown increasing potential as new therapeutic targets. As a consequence, PPIs are today the most screened target class in high-throughput screening (HTS). The development of broad chemical libraries dedicated to these particular targets is essential; however, the chemical space associated with this 'high-hanging fruit' is still under debate. Here, we analyse the properties of 40 non-redundant small molecules present in the 2P2I database (http://2p2idb.cnrs-mrs.fr/) to define a general profile of orthosteric inhibitors and propose an original protocol to filter general screening libraries using a support vector machine (SVM) with 11 standard Dragon molecular descriptors. The filtering protocol has been validated using external datasets from PubChem BioAssay and results from in-house screening campaigns. This external blind validation demonstrated the ability of the SVM model to reduce the size of the filtered chemical library by eliminating up to 96% of the compounds as well as enhancing the proportion of active compounds by up to a factor of 8. We believe that the resulting chemical space identified in this paper will provide the scientific community with a concrete support to search for PPI inhibitors during HTS campaigns.
- Published
- 2013
- Full Text
- View/download PDF
28. Coordinate Transcriptomic and Metabolomic Effects of the Insulin Sensitizer Rosiglitazone on Fundamental Metabolic Pathways in Liver, Soleus Muscle, and Adipose Tissue in Diabetic db/db Mice.
- Author
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Le Bouter S, Rodriguez M, Guigal-Stephan N, Courtade-Gaïani S, Xuereb L, de Montrion C, Croixmarie V, Umbdenstock T, Boursier-Neyret C, Lonchampt M, Brun M, Dacquet C, Ktorza A, Lockhart BP, and Galizzi JP
- Abstract
Rosiglitazone (RSG), developed for the treatment of type 2 diabetes mellitus, is known to have potent effects on carbohydrate and lipid metabolism leading to the improvement of insulin sensitivity in target tissues. To further assess the capacity of RSG to normalize gene expression in insulin-sensitive tissues, we compared groups of 18-day-treated db/db mice with increasing oral doses of RSG (10, 30, and 100 mg/kg/d) with untreated non-diabetic littermates (db/+). For this aim, transcriptional changes were measured in liver, inguinal adipose tissue (IAT) and soleus muscle using microarrays and real-time PCR. In parallel, targeted metabolomic assessment of lipids (triglycerides (TGs) and free fatty acids (FFAs)) in plasma and tissues was performed by UPLC-MS methods. Multivariate analyses revealed a relationship between the differential gene expressions in liver and liver trioleate content and between blood glucose levels and a combination of differentially expressed genes measured in liver, IAT, and muscle. In summary, we have integrated gene expression and targeted metabolomic data to present a comprehensive overview of RSG-induced changes in a diabetes mouse model and improved the molecular understanding of how RSG ameliorates diabetes through its effect on the major insulin-sensitive tissues.
- Published
- 2010
- Full Text
- View/download PDF
29. Novel hexad repeats conserved in a putative transporter with restricted expression in cell types associated with growth, calcium exchange and homeostasis.
- Author
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Brasier G, Tikellis C, Xuereb L, Craigie J, Casley D, Kovacs CS, Fudge NJ, Kalnins R, Cooper ME, and Wookey PJ
- Subjects
- Amino Acid Sequence, Animals, Animals, Newborn, Conserved Sequence, Female, Homeostasis, Humans, Kidney chemistry, Kidney embryology, Membrane Transport Proteins metabolism, Mice, Mice, Inbred C57BL, Molecular Sequence Data, Pituitary Gland chemistry, Pituitary Gland cytology, Pituitary Gland metabolism, Placenta chemistry, Protein Structure, Secondary, Protein Structure, Tertiary, RNA, Messenger genetics, RNA, Messenger metabolism, Rats, Rats, Sprague-Dawley, Sequence Homology, Amino Acid, Tissue Distribution, Calcium metabolism, Cell Division, Membrane Transport Proteins chemistry
- Abstract
A transport protein is described with 12 transmembrane spans. Within the cytoplasmic amino-terminal domain, several novel hexad repeats are conserved in human, mouse, rat and pig, four to six of which had the canonical form PS_S_H(+). In the carboxyl-terminal domain, a polyglutamate sequence (5-8) is conserved. Restricted expression of the transporter was identified in acidophil cells of the adult pituitary that secrete growth hormone and prolactin. In the fetus, expression was restricted to osteoclasts, chondrocytes, thyroid, pituitary, central nervous system, eye, liver and heart. In particular, expression was found in structures associated with rapid calcium exchange including the retina, cardiomyocytes and in the intraplacental yolk sac that expresses calcitropic molecules. Furthermore, expression found in osteoclasts and kidney, within the distal portions of nephrons and collecting ducts, was consistent with a role in calcium homeostasis. In human pituitary, four mRNA transcripts, and in mouse kidney, three mRNA transcripts were expressed. In developing mouse kidney, the amount of each transcript varied that suggested the multiple transcripts might be differentially expressed in different physiological states. We propose that the transporter is specific for a calcium-chelator complex and is important for growth and calcium metabolism.
- Published
- 2004
- Full Text
- View/download PDF
30. Amylin in the periphery.
- Author
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Wookey PJ, Xuereb L, Tikellis C, and Cooper ME
- Subjects
- Animals, Humans, Islet Amyloid Polypeptide, Amyloid physiology
- Abstract
Amylin (islet amyloid polypeptide) is a peptide synthesized principally in the beta-cells of the pancreatic islets together with insulin and has actions as a hormone, growth factor, and modifier of behavior. As a hormone, amylin acts to modify gastric motility, renal resorption, and has metabolic actions. It is postulated that the principal function of amylin as a hormone is the activation of physiological processes associated with feeding. As a growth factor, amylin acts on bone cells, renal proximal tubular cells, and islet beta-cells. Amylin has important targets in the brain that mediate its actions in the modification of behavior, including thirst and satiety. In man, amylin can form islet amyloid deposits, an event linked to the reduction of b-cell mass and loss of signal-secretion coupling. Recent evidence has defined a new role for monomeric amylin as a growth factor and regulator of beta-cell mass that is postulated to be a key factor in pathophysiological processes that result in overt diabetes.
- Published
- 2003
- Full Text
- View/download PDF
31. Calcitonin receptor isoforms expressed in the developing rat kidney.
- Author
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Tikellis C, Xuereb L, Casley D, Brasier G, Cooper ME, and Wookey PJ
- Subjects
- Aging metabolism, Amyloid metabolism, Animals, Autoradiography, Binding Sites, Embryo, Mammalian physiology, Embryonic and Fetal Development, Immunohistochemistry, Islet Amyloid Polypeptide, Kidney growth & development, Kidney Cortex metabolism, Kidney Medulla metabolism, Molecular Weight, Protein Isoforms metabolism, Rats, Rats, Sprague-Dawley, Receptors, Calcitonin chemistry, Tissue Distribution, Animals, Newborn growth & development, Animals, Newborn metabolism, Kidney embryology, Kidney metabolism, Receptors, Calcitonin metabolism
- Abstract
Background: Development in the metanephric-kidney transition period involves the precise expression of paracrine and autocrine events in an ordered spatio-temporal manner. Expression of these molecular events is tightly controlled and includes positive and negative growth factors and cognate receptors within close proximity in developing structures in the expanding renal cortex and medulla. The expression of calcitonin receptor (CTR) isoforms C1a and C1b in this context has not previously been described. Our current study also explored the relationship between the expression of CTR isoforms and amylin binding sites., Methods: Techniques included immunohistochemistry with novel antibodies that detect CTR isoforms, real time PCR for the quantification of CTR isoforms, Western blot and in vitro autoradiography, on tissues from embryo day 18 to postnatal day 30., Results: The CTR C1a isoform is expressed in the ureteric ducts of the metanephros and both isoforms are expressed in the developing distal convoluted tubules, ascending limbs of the loop of Henle and collecting ducts in the postnatal rat kidney. There was a 60-fold excess of C1a versus C1b isoforms. An apparent molecular weight of 63 kD was found. In vitro autoradiography demonstrated that while amylin binding sites were predominantly in the cortex, CTR expression was largely localized in the medulla in an earlier event, followed by cortical expression., Conclusions: CTR C1a protein expression has been identified in the ureteric ducts in the metanephros and both isoforms expressed in the distal portions of the developing nephrons and collecting ducts. Since amylin binding sites have been localized on the proximal tubules of the cortex, it is unlikely that amylin receptors can be represented by modification of CTR affinity with receptor activity modifying proteins in the kidney.
- Published
- 2003
- Full Text
- View/download PDF
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