Research Output

Article

Activated prothrombin complex concentrate (FEIBA(®) ) in acquired haemophilia A: a large multicentre Italian study - the FAIR Registry

Zanon, E., Pasca, S., Santoro, C., Gamba, G., Siragusa, S. M., Rocino, A., Cantori, I., Federici, A. B., Mameli, L., Giuffrida, G., Falanga, A., Lodigiani, C., Santoro, R. C., Milan, M., Ambaglio, C., Napolitano, M. & Mazzucconi, M. G., Mar 2019, In : British Journal of Haematology. 184, 5, p. 853-855 3 p.

Research output: Contribution to journalArticle

Activated prothrombin complex concentrate (FEIBA®) in acquired haemophilia A: A large multicentre Italian study - the FAIR Registry

Zanon, E., Pasca, S., Santoro, C., Gamba, G., Siragusa, S. M., Rocino, A., Cantori, I., Federici, A. B., Mameli, L., Giuffrida, G., Falanga, A., Lodigiani, C., Santoro, R. C., Milan, M., Ambaglio, C., Napolitano, M. & Mazzucconi, M. G., Jan 1 2018, (Accepted/In press) In : British Journal of Haematology.

Research output: Contribution to journalArticle

Activating mutations of the G(s)α gene are associated with low levels of Gsα protein in growth hormone-secreting tumors

Ballaré, E., Mantovani, S., Lania, A., Di Blasio, A. M., Vallar, L. & Spada, A., 1998, In : Journal of Clinical Endocrinology and Metabolism. 83, 12, p. 4386-4390 5 p.

Research output: Contribution to journalArticle

Activation effects of a prion protein fragment [PrP-(106-126)] on human leucocytes

Diomede, L., Sozzani, S., Luini, W., Algeri, M., De Gioia, L., Chiesa, R., Lievens, P. M. J., Bugiani, O., Forloni, G., Tagliavini, F. & Salmona, M., Dec 1 1996, In : Biochemical Journal. 320, 2, p. 563-570 8 p.

Research output: Contribution to journalArticle

Activation of cAMP-PKA signaling in vivo inhibits smooth muscle cell proliferation induced by vascular injury

Indolfi, C., Avvedimento, E. V., Di Lorenzo, E., Esposito, G., Rapacciuolo, A., Giuliano, P., Grieco, D., Cavuto, L., Stingone, A. M., Ciullo, I., Condorelli, G. & Chiariello, M., Jul 1997, In : Nature Medicine. 3, 7, p. 775-781 7 p.

Research output: Contribution to journalArticle

Activation of cardiac progenitor cells reverses the failing heart senescent phenotype and prolongs lifespan

Gonzalez, A., Rota, M., Nurzynska, D., Misao, Y., Tillmanns, J., Ojaimi, C., Padin-Iruegas, M. E., Müller, P., Esposito, G., Bearzi, C., Vitale, S., Dawn, B., Sanganalmath, S. K., Baker, M., Hintze, T. H., Bolli, R., Urbanek, K., Hosoda, T., Anversa, P., Kajstura, J. & 1 others, Leri, A., Mar 2008, In : Circulation Research. 102, 5, p. 597-606 10 p.

Research output: Contribution to journalArticle

Activation of double-stranded RNA dependent protein kinase by ribosomal RNA precursors

Bottazzi, B., Clayton, M. & Varesio, L., Oct 1987, In : Cytotechnology. 1, 1, p. 57-60 4 p.

Research output: Contribution to journalArticle

Activation of ERBB2 signaling causes resistance to the EGFR-directed therapeutic antibody cetuximab

Yonesaka, K., Zejnullahu, K., Okamoto, I., Satoh, T., Cappuzzo, F., Souglakos, J., Ercan, D., Rogers, A., Roncalli, M., Takeda, M., Fujisaka, Y., Philips, J., Shimizu, T., Maenishi, O., Cho, Y., Sun, J., Destro, A., Taira, K., Takeda, K., Okabe, T. & 12 others, Swanson, J., Itoh, H., Takada, M., Lifshits, E., Okuno, K., Engelman, J. A., Shivdasani, R. A., Nishio, K., Fukuoka, M., Varella-Garcia, M., Nakagawa, K. & Jänne, P. A., Sep 7 2011, In : Science Translational Medicine. 3, 99

Research output: Contribution to journalArticle

Activation of ERBB2 signaling causes resistance to the EGFR-directed therapeutic antibody cetuximab.

Yonesaka, K., Zejnullahu, K., Okamoto, I., Satoh, T., Cappuzzo, F., Souglakos, J., Ercan, D., Rogers, A., Roncalli, M., Takeda, M., Fujisaka, Y., Philips, J., Shimizu, T., Maenishi, O., Cho, Y., Sun, J., Destro, A., Taira, K., Takeda, K., Okabe, T. & 12 others, Swanson, J., Itoh, H., Takada, M., Lifshits, E., Okuno, K., Engelman, J. A., Shivdasani, R. A., Nishio, K., Fukuoka, M., Varella-Garcia, M., Nakagawa, K. & Jänne, P. A., Sep 7 2011, In : Science Translational Medicine. 3, 99

Research output: Contribution to journalArticle

Activation of JAK2 in human vascular endothelial cells by granulocyte- macrophage colony-stimulating factor

Soldi, R., Primo, L., Brizzi, M. F., Sanavio, F., Aglietta, M., Polentarutti, N., Pegoraro, L., Mantovani, A. & Bussolino, F., Feb 1 1997, In : Blood. 89, 3, p. 863-872 10 p.

Research output: Contribution to journalArticle

Activation of K cells in mice with transplanted tumours differing in immunogenicity and metastasizing capacity

Mantovani, A., Polentarutti, N., Alessandri, G., Vecchi, A., Giuliani, F. & Spreafico, F., 1977, In : British Journal of Cancer. 36, 4, p. 453-460 8 p.

Research output: Contribution to journalArticle

Activation of leukemia-associated RhoGEF by Gα13 with significant conformational rearrangements in the interface

Suzuki, N., Tsumoto, K., Hajicek, N., Daigo, K., Tokita, R., Minami, S., Kodama, T., Hamakubo, T. & Kozasa, T., Feb 20 2009, In : Journal of Biological Chemistry. 284, 8, p. 5000-5009 10 p.

Research output: Contribution to journalArticle

Activation of NF-κB by IL-1β blocks IL-6-induced sustained STAT3 activation and STAT3-dependent gene expression of the human γ-fibrinogen gene

Albrecht, U., Yang, X., Asselta, R., Keitel, V., Tenchini, M. L., Ludwig, S., Heinrich, P. C., Häussinger, D., Schaper, F. & Bode, J. G., Sep 2007, In : Cellular Signalling. 19, 9, p. 1866-1878 13 p.

Research output: Contribution to journalArticle

Activation of nuclear factor of activated T cells in a cyclosporin A- resistant pathway

Ghosh, P., Sica, A., Cippitelli, M., Subleski, J., Lahesmaa, R., Young, H. A. & Rice, N. R., 1996, In : Journal of Biological Chemistry. 271, 13, p. 7700-7704 5 p.

Research output: Contribution to journalArticle

Activation of phospholipase D by interleukin-8 in human neutrophils

Sozzani, S., Agwu, D. E., Ellenburg, M. D., Locati, M., Rieppi, M., Rojas, A., Mantovani, A. & McPhail, L. C., Dec 1 1994, In : Blood. 84, 11, p. 3895-3901 7 p.

Research output: Contribution to journalArticle

Activation of signal transducer and activator of transcription 3 in rat liver after heat shock and reperfusion stress

Tacchini, L., Fusar-Poli, D., Sironi, M., Mantovani, A. & Bernelli-Zazzera, A., Mar 1 2003, In : International Journal of Biochemistry and Cell Biology. 35, 3, p. 316-323 8 p.

Research output: Contribution to journalArticle

Activation of the contact system and inflammation after thrombolytic therapy in patients with acute myocardial infarction

Merlini, P. A., Cugno, M., Rossi, M. L., Agricola, P., Repetto, A., Fetiveau, R., Diotallevi, P., Canosi, U., Mannucci, P. M. & Ardissino, D., Apr 1 2004, In : The American Journal of Cardiology. 93, 7, p. 822-825 4 p.

Research output: Contribution to journalArticle

Activation of the Pro-Oxidant PKCβII-p66Shc Signaling Pathway Contributes to Pericyte Dysfunction in Skeletal Muscles of Patients With Diabetes With Critical Limb Ischemia

Vono, R., Fuoco, C., Testa, S., Pirrò, S., Maselli, D., Ferland McCollough, D., Sangalli, E., Pintus, G., Giordo, R., Finzi, G., Sessa, F., Cardani, R., Gotti, A., Losa, S., Cesareni, G., Rizzi, R., Bearzi, C., Cannata, S., Spinetti, G., Gargioli, C. & 1 others, Madeddu, P., Dec 2016, In : Diabetes. 65, 12, p. 3691-3704 14 p.

Research output: Contribution to journalArticle

Activation of the VEGFC/VEGFR3 Pathway Induces Tumor Immune Escape in Colorectal Cancer

Tacconi, C., Ungaro, F., Correale, C., Arena, V., Massimino, L., Detmar, M., Spinelli, A., Carvello, M., Mazzone, M., Oliveira, A. I., Rubbino, F., Garlatti, V., Spanò, S., Lugli, E., Colombo, F. S., Malesci, A., Peyrin-Biroulet, L., Vetrano, S., Danese, S. & D'Alessio, S., Aug 15 2019, In : Cancer Research. 79, 16, p. 4196-4210 15 p.

Research output: Contribution to journalArticle

Activation of the Wnt-βcatenin pathway in a cell population on the surface of the forebrain is essential for the establishment of olfactory axon connections

Zaghetto, A. A., Paina, S., Mantero, S., Platonova, N., Peretto, P., Bovetti, S., Puche, A., Piccolo, S. & Merlo, G. R., Sep 5 2007, In : Journal of Neuroscience. 27, 36, p. 9757-9768 12 p.

Research output: Contribution to journalArticle

Activation or inactivation of cardiac Akt/mTOR signaling diverges physiological from pathological hypertrophy

Kemi, O. J., Ceci, M., Wisloff, U., Grimaldi, S., Gallo, P., Smith, G. L., Condorelli, G. & Ellingsen, O., Feb 2008, In : Journal of Cellular Physiology. 214, 2, p. 316-321 6 p.

Research output: Contribution to journalArticle

"Active" cancer immunotherapy by anti-met antibody gene transfer

Vigna, E., Pacchiana, G., Mazzone, M., Chiriaco, C., Fontani, L., Basilico, C., Pennacchietti, S. & Comoglio, P. M., Nov 15 2008, In : Cancer Research. 68, 22, p. 9176-9183 8 p.

Research output: Contribution to journalArticle

Active endocannabinoids are secreted on extracellular membrane vesicles

Gabrielli, M., Battista, N., Riganti, L., Prada, I., Antonucci, F., Cantone, L., Matteoli, M., Maccarrone, M. & Verderio, C., Feb 1 2015, In : EMBO Reports. 16, 2, p. 213-220 8 p.

Research output: Contribution to journalArticle

Active endocannabinoids are secreted on the surface of microglial microvesicles

Gabrielli, M., Battista, N., Riganti, L., Prada, I., Antonucci, F., Cantone, L., Lombardi, M., Matteoli, M., Maccarrone, M. & Verderio, C., Dec 1 2015, In : SpringerPlus. 4, p. 1-32 32 p., L29.

Research output: Contribution to journalArticle

Active surveillance for low-risk non-muscle-invasive bladder cancer: Mid-term results from the Bladder cancer Italian Active Surveillance (BIAS) project.

Hurle, R., Pasini, L., Lazzeri, M., Colombo, P., Buffi, N., Lughezzani, G., Casale, P., Morenghi, E., Peschechera, R., Zandegiacomo, S., Benetti, A., Saita, A., Cardone, P. & Guazzoni, G., 2016, (Accepted/In press) In : BJU International.

Research output: Contribution to journalArticle

Active Surveillance for Low Risk Nonmuscle Invasive Bladder Cancer: A Confirmatory and Resource Consumption Study from the BIAS Project

Hurle, R., Lazzeri, M., Vanni, E., Vanni, E., Lughezzani, G., Casale, P., Saita, A., Morenghi, E., Morenghi, E., Forni, G., Cardone, P., Lista, G., Colombo, P., Peschechera, R., Pasini, L., Zandegiacomo, S., Benetti, A., Maffei, D., Vavassori, I., Guazzoni, G. & 1 others, Buffi, N. M., Feb 1 2018, In : Journal of Urology. 199, 2, p. 401-406 6 p.

Research output: Contribution to journalArticle

Activin a as a mediator of nk-dendritic cell functional interactions

Seeger, P., Bosisio, D., Parolini, S., Badolato, R., Gismondi, A., Santoni, A. & Sozzani, S., Feb 1 2014, In : Journal of Immunology. 192, 3, p. 1241-1248 8 p.

Research output: Contribution to journalArticle

Activin A induces dendritic cell migration through the polarized release of CXC chemokine ligands 12 and 14

Salogni, L., Musso, T., Bosisio, D., Mirolo, M., Jala, V. R., Haribabu, B., Locati, M. & Sozzani, S., 2009, In : Blood. 113, 23, p. 5848-5856 9 p.

Research output: Contribution to journalArticle

Activin A induces langerhans cell differentiation in vitro and in human skin explants

Musso, T., Scutera, S., Vermi, W., Daniele, R., Fornaro, M., Castagnoli, C., Alotto, D., Ravanini, M., Cambieri, I., Salogni, L., Elia, A. R., Giovarelli, M., Facchetti, F., Girolomoni, G. & Sozzani, S., Sep 24 2008, In : PLoS One. 3, 9, e3271.

Research output: Contribution to journalArticle

Activity and function of the nuclear factor kappaB pathway in human parathyroid tumors

Corbetta, S., Vicentini, L., Ferrero, S., Lania, A., Mantovani, G., Cordella, D., Beck-Peccoz, P. & Spada, A., Dec 2005, In : Endocrine-Related Cancer. 12, 4, p. 929-937 9 p.

Research output: Contribution to journalArticle

Activity and safety of ceritinib in patients with ALK-rearranged non-small-cell lung cancer (ASCEND-1): Updated results from the multicentre, open-label, phase 1 trial

Kim, D. W., Mehra, R., Tan, D. S. W., Felip, E., Chow, L. Q. M., Camidge, D. R., Vansteenkiste, J., Sharma, S., De Pas, T., Riely, G. J., Solomon, B., Wolf, J., Thomas, M., Schuler, M., Liu, G., Santoro, A., Sutradhar, S., Li, S., Szczudlo, T., Yovine, A. & 1 others, Shaw, A. T., 2016, (Accepted/In press) In : The Lancet Oncology.

Research output: Contribution to journalArticle

Activity and safety of ceritinib in patients with ALK-rearranged non-small-cell lung cancer (ASCEND-1): Updated results from the multicentre, open-label, phase 1 trial

Kim, D. W., Mehra, R., Tan, D. S. W., Felip, E., Chow, L. Q. M., Camidge, D. R., Vansteenkiste, J., Sharma, S., De Pas, T., Riely, G. J., Solomon, B. J., Wolf, J., Thomas, M., Schuler, M., Liu, G., Santoro, A., Sutradhar, S., Li, S., Szczudlo, T., Yovine, A. & 1 others, Shaw, A. T., 2016, (Accepted/In press) In : The Lancet Oncology.

Research output: Contribution to journalArticle

Activity and safety of NGR-hTNF, a selective vascular-targeting agent, in previously treated patients with advanced hepatocellular carcinoma

Santoro, A., Pressiani, T., Citterio, G., Rossoni, G., Donadoni, G., Pozzi, F., Rimassa, L., Personeni, N., Bozzarelli, S., Rossoni, G., Colombi, S., De Braud, F. G., Caligaris-Cappio, F., Lambiase, A. & Bordignon, C., Sep 7 2010, In : British Journal of Cancer. 103, 6, p. 837-844 8 p.

Research output: Contribution to journalArticle

Activity-dependent phosphorylation of Ser187 is required for SNAP-25-negative modulation of neuronal voltage-gated calcium channels

Pozzi, D., Condliffe, S., Bozzi, Y., Chikhladze, M., Grumelli, C., Proux-Gillardeaux, V., Takahashi, M., Franceschetti, S., Verderio, C. & Matteoli, M., Jan 8 2008, In : Proceedings of the National Academy of Sciences of the United States of America. 105, 1, p. 323-328 6 p.

Research output: Contribution to journalArticle

Activity of 4-HPR in superficial bladder cancer using DNA flow cytometry as an intermediate endpoint

Decensi, A., Bruno, S., Giaretti, W., Torrisi, R., Curotto, A., Gatteschi, B., Geido, E., Polizzi, A., Costantini, M., Bruzzi, P., Nicolo, G., Costa, A., Boccardo, F., Giuliani, L. & Santi, L., 1992, In : Journal of Cellular Biochemistry. 50, SUPPL. 16 I, p. 139-147 9 p.

Research output: Contribution to journalArticle

Activity of a specific inhibitor, gefitinib (Iressa™, ZD1839), of epidermal growth factor receptor in refractory non-smal-cell lung cancer

Santoro, A., Cavina, R., Latteri, F., Zucali, P. A., Ginanni, V., Campagnoli, E., Ferrari, B., Morenghi, E., Pedicini, V., Roncalli, M., Alloisio, M., Ravasi, G. & Soto Parra, H. J., Jan 2004, In : Annals of Oncology. 15, 1, p. 33-37 5 p.

Research output: Contribution to journalArticle

Activity of EGFR TKIs in Caucasian Patients With NSCLC Harboring Potentially Sensitive Uncommon EGFR Mutations

Passaro, A., Prelaj, A., Bonanno, L., Tiseo, M., Tuzi, A., Proto, C., Chiari, R., Rocco, D., Genova, C., Sini, C., Cortinovis, D., Pilotto, S., Landi, L., Bennati, C., Camerini, A., Toschi, L., Putzu, C., Cerea, G., Spitaleri, G., Cappuzzo, F. & 1 others, de Marinis, F., Mar 1 2019, In : Clin. Lung Cancer. 20, 2, p. e186-e194

Research output: Contribution to journalArticle

Activity of EGFR TKIs in Caucasian Patients With NSCLC Harboring Potentially Sensitive Uncommon EGFR Mutations: Clinical Lung Cancer

Passaro, A., Prelaj, A., Bonanno, L., Tiseo, M., Tuzi, A., Proto, C., Chiari, R., Rocco, D., Genova, C., Sini, C., Cortinovis, D., Pilotto, S., Landi, L., Bennati, C., Camerini, A., Toschi, L., Putzu, C., Cerea, G., Spitaleri, G., Cappuzzo, F. & 1 others, de Marinis, F., 2019, In : Clin. Lung Cancer. 20, 2, p. e186-e194

Research output: Contribution to journalArticle

Activity of EGFR TKIs in Caucasian Patients With NSCLC Harboring Potentially Sensitive Uncommon EGFR Mutations

Passaro, A., Prelaj, A., Bonanno, L., Tiseo, M., Tuzi, A., Proto, C., Chiari, R., Rocco, D., Genova, C., Sini, C., Cortinovis, D., Pilotto, S., Landi, L., Bennati, C., Camerini, A., Toschi, L., Putzu, C., Cerea, G., Spitaleri, G., Cappuzzo, F. & 1 others, de Marinis, F., 2019, In : Clinical Lung Cancer. 20, 2, p. e186-e194

Research output: Contribution to journalArticle

Activity of EGFR TKIs in Caucasian Patients With NSCLC Harboring Potentially Sensitive Uncommon EGFR Mutations

Passaro, A., Prelaj, A., Bonanno, L., Tiseo, M., Tuzi, A., Proto, C., Chiari, R., Rocco, D., Genova, C., Sini, C., Cortinovis, D., Pilotto, S., Landi, L., Bennati, C., Camerini, A., Toschi, L., Putzu, C., Cerea, G., Spitaleri, G., Cappuzzo, F. & 1 others, de Marinis, F., Mar 1 2019, In : Clinical Lung Cancer. 20, 2, p. e186-e194

Research output: Contribution to journalArticle

Activity of EGFR TKIs in Caucasian Patients With NSCLC Harboring Potentially Sensitive Uncommon EGFR Mutations

Passaro, A., Prelaj, A., Bonanno, L., Tiseo, M., Tuzi, A., Proto, C., Chiari, R., Rocco, D., Genova, C., Sini, C., Cortinovis, D., Pilotto, S., Landi, L., Bennati, C., Camerini, A., Toschi, L., Putzu, C., Cerea, G., Spitaleri, G., Cappuzzo, F. & 1 others, de Marinis, F., Nov 20 2018, In : Clinical Lung Cancer. 9 p.

Research output: Contribution to journalArticle

Activity of Pemetrexed on brain metastases from Non-Small Cell Lung Cancer

Bearz, A., Garassino, I., Tiseo, M., Caffo, O., Soto-Parra, H., Boccalon, M., Talamini, R., Santoro, A., Bartolotti, M., Murgia, V., Berretta, M. & Tirelli, U., May 2010, In : Lung Cancer. 68, 2, p. 264-268 5 p.

Research output: Contribution to journalArticle

Activity of single agent vinorelbine in pretreated non-Hodgkin's lymphoma

Balzarotti, M., Santoro, A., Tondini, C., Fornier, M. & Bonadonna, G., Nov 1996, In : Annals of Oncology. 7, 9, p. 970-972 3 p.

Research output: Contribution to journalArticle

Activity of Trifluoperazine against Replicating, Non-Replicating and Drug Resistant M. tuberculosis

Advani, M. J., Siddiqui, I., Sharma, P. & Reddy, H., Aug 31 2012, In : PLoS One. 7, 8, e44245.

Research output: Contribution to journalArticle

Acute and 30-Day Outcomes in Women After TAVR: Results From the WIN-TAVI (Women's INternational Transcatheter Aortic Valve Implantation) Real-World Registry

Chieffo, A., Petronio, A. S., Mehilli, J., Chandrasekhar, J., Sartori, S., Lefèvre, T., Presbitero, P., Capranzano, P., Tchetche, D., Iadanza, A., Sardella, G., van Mieghem, N. M., Meliga, E., Dumonteil, N., Fraccaro, C., Trabattoni, D., Mikhail, G. W., Sharma, S., Ferrer, M. C., Naber, C. & 6 others, Kievit, P., Faggioni, M., Snyder, C., Morice, M. C., Mehran, R. & Rossi, M. L., Aug 8 2016, In : JACC: Cardiovascular Interventions. 9, 15, p. 1589-1600 12 p.

Research output: Contribution to journalArticle

Acute and 30-Day Outcomes in Women After TAVR: Results From the WIN-TAVI (Women's INternational Transcatheter Aortic Valve Implantation) Real-World Registry

Chieffo, A., Petronio, A. S., Mehilli, J., Chandrasekhar, J., Sartori, S., Lefèvre, T., Presbitero, P., Capranzano, P., Tchetche, D., Iadanza, A., Sardella, G., van Mieghem, N. M., Meliga, E., Dumonteil, N., Fraccaro, C., Trabattoni, D., Mikhail, G. W., Sharma, S., Ferrer, M. C., Naber, C. & 5 others, Kievit, P., Faggioni, M., Snyder, C., Morice, M. C. & Mehran, R., Aug 8 2016, In : JACC: Cardiovascular Interventions. 9, 15, p. 1589-1600 12 p.

Research output: Contribution to journalArticle

Acute and 30-Day Outcomes in Women After TAVR: Results From the WIN-TAVI (Women's INternational Transcatheter Aortic Valve Implantation) Real-World Registry

Chieffo, A., Petronio, A. S., Mehilli, J., Chandrasekhar, J., Sartori, S., Lefèvre, T., Presbitero, P., Capranzano, P., Tchetche, D., Iadanza, A., Sardella, G., Van Mieghem, N. M., Meliga, E., Dumonteil, N., Fraccaro, C., Trabattoni, D., Mikhail, G. W., Sharma, S., Ferrer, M. C., Naber, C. & 5 others, Kievit, P., Faggioni, M., Snyder, C., Morice, M. C. & Mehran, R., Aug 8 2016, In : JACC: Cardiovascular Interventions. 9, 15, p. 1589-1600 12 p.

Research output: Contribution to journalArticle

Acute and long-term (2-years) clinical outcomes of the CoreValve 31mm in large aortic annuli: A multicenter study

Attizzani, G. F., Ohno, Y., Latib, A., Petronio, A. S., Giannini, C., Ettori, F., Curello, S., Bedogni, F., Todaro, D., Brambilla, N., Bruschi, G., Colombo, P., Presbitero, P., Fiorilli, R., Poli, A., Martina, P., Colombo, A., Barbanti, M. & Tamburino, C., Jan 15 2017, In : International Journal of Cardiology. 227, p. 543-549 7 p.

Research output: Contribution to journalArticle