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60. A new prognostic clinicopathological classification of pituitary adenomas: a multicentric case–control study of 410 patients with 8 years post-operative follow-up

Author

Trouillas, Jacqueline, Roy, Pascal, Sturm, Nathalie, Dantony, Emmanuelle, Cortet-Rudelli, Christine, Viennet, Gabriel, Bonneville, Jean-François, Assaker, Richard, Auger, Carole, Brue, Thierry, Cornelius, Aurélie, Dufour, Henry, Jouanneau, Emmanuel, François, Patrick, Galland, Françoise, Mougel, François, Chapuis, François, Villeneuve, Laurent, Maurage, Claude-Alain, Figarella-Branger, Dominique, Raverot, Gérald, Barlier, Anne, Bernier, M., Bonnet, Fabrice, Borson-Chazot, F., Brassier, Gilles, Caulet-Maugendre, S., Chabre, O., Chanson, P., Cottier, J. F., Delemer, B., Delgrange, E., Di Tommaso, L., Eimer, S., Gaillard, Sophie, Jan, M., Girard, J. J., Lapras, V., Loiseau, H., Passagia, J. G., Patey, M., Penfornis, A., Poirier, J. Y., Perrin, G., Tabarin, A., Centre de recherche en neurosciences de Lyon (CRNL), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Université Jean Monnet [Saint-Étienne] (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Biostatistiques santé, Département biostatistiques et modélisation pour la santé et l'environnement [LBBE], Laboratoire de Biométrie et Biologie Evolutive - UMR 5558 (LBBE), Université de Lyon-Université de Lyon-Institut National de Recherche en Informatique et en Automatique (Inria)-VetAgro Sup - Institut national d'enseignement supérieur et de recherche en alimentation, santé animale, sciences agronomiques et de l'environnement (VAS)-Centre National de la Recherche Scientifique (CNRS)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de Recherche en Informatique et en Automatique (Inria)-VetAgro Sup - Institut national d'enseignement supérieur et de recherche en alimentation, santé animale, sciences agronomiques et de l'environnement (VAS)-Centre National de la Recherche Scientifique (CNRS)-Laboratoire de Biométrie et Biologie Evolutive - UMR 5558 (LBBE), Université de Lyon-Université de Lyon-Institut National de Recherche en Informatique et en Automatique (Inria)-VetAgro Sup - Institut national d'enseignement supérieur et de recherche en alimentation, santé animale, sciences agronomiques et de l'environnement (VAS)-Centre National de la Recherche Scientifique (CNRS), Estrogènes, Expression génique et pathologies du Système Nerveux Central - UFC (E2SNC / ESTROGENES), Université de Franche-Comté (UFC), Université Bourgogne Franche-Comté [COMUE] (UBFC)-Université Bourgogne Franche-Comté [COMUE] (UBFC), IFR des neurosciences de Lyon (IFNL), Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre Hospitalier le Vinatier [Bron]-Hospices Civils de Lyon (HCL)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon, Centre de recherche en neurobiologie - neurophysiologie de Marseille (CRN2M), Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Service d'endocrinologie diabétologie et nutrition [Rennes], Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-CHU Pontchaillou [Rennes]-Hôpital Anne-de-Bretagne, Service de Diabétologie - Endocrinologie [CHRU Besançon], Centre Hospitalier Régional Universitaire de Besançon (CHRU Besançon), Unité de Méthodologie en Recherche Clinique, Université de Lyon-Université de Lyon-Hospices Civils de Lyon (HCL), Centre de Recherche Jean-Pierre AUBERT Neurosciences et Cancer - U1172 Inserm - U837 (JPArc), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Lille Nord de France (COMUE)-Université de Lille, Centre de Recherches en Oncologie biologique et Oncopharmacologie (CRO2), Institut National de la Santé et de la Recherche Médicale (INSERM)- Hôpital de la Timone [CHU - APHM] (TIMONE)-Aix Marseille Université (AMU), Centre Hospitalier Universitaire (Rennes), Foie, métabolismes et cancer, Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), Service de neurochirurgie [Rennes] = Neurosurgery [Rennes], CHU Pontchaillou [Rennes], Institut de recherche en santé, environnement et travail (Irset), Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique )-Institut National de la Santé et de la Recherche Médicale (INSERM)-École des Hautes Études en Santé Publique [EHESP] (EHESP)-Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Université d'Angers (UA), Centre de recherche en neurosciences de Lyon - Lyon Neuroscience Research Center (CRNL), Université de Lyon-Université de Lyon-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Service de Biostatistiques [Lyon], Hospices Civils de Lyon (HCL), Université de Lyon-Université de Lyon-Hospices Civils de Lyon (HCL)-Centre Hospitalier le Vinatier [Bron]-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Université de Rennes (UR)-CHU Pontchaillou [Rennes]-Hôpital Anne-de-Bretagne, Centre de Recherche Jean-Pierre AUBERT Neurosciences et Cancer - U837 (JPArc), Université Lille Nord de France (COMUE)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille, Aix Marseille Université (AMU)- Hôpital de la Timone [CHU - APHM] (TIMONE)-Institut National de la Santé et de la Recherche Médicale (INSERM), Université de Rennes (UR)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), and Université d'Angers (UA)-Université de Rennes (UR)-École des Hautes Études en Santé Publique [EHESP] (EHESP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique )

Subjects
Adult, Male, medicine.medical_specialty, Pathology, Adolescent, 030209 endocrinology & metabolism, Disease, Sensitivity and Specificity, Gastroenterology, Disease-Free Survival, Pathology and Forensic Medicine, Young Adult, 03 medical and health sciences, Cellular and Molecular Neuroscience, Sex Factors, 0302 clinical medicine, Recurrence, Pituitary adenoma, Internal medicine, medicine, Humans, Endocrine system, Pituitary Neoplasms, Longitudinal Studies, Young adult, Atypical Adenoma, Aged, Retrospective Studies, medicine.diagnostic_test, Pituitary tumour, business.industry, Age Factors, Case-control study, [SDV.MHEP.HEG]Life Sciences [q-bio]/Human health and pathology/Hépatology and Gastroenterology, Magnetic resonance imaging, Retrospective cohort study, Middle Aged, Prognosis, Classification, medicine.disease, Magnetic Resonance Imaging, 3. Good health, Case-Control Studies, Pituitary Gland, Female, Neurology (clinical), business, 030217 neurology & neurosurgery
Abstract

International audience; Pituitary adenomas are currently classified by histological, immunocytochemical and numerous ultrastructural characteristics lacking unequivocal prognostic correlations. We investigated the prognostic value of a new clinicopathological classification with grades based on invasion and proliferation. This retrospective multicentric case-control study comprised 410 patients who had surgery for a pituitary tumour with long-term follow-up. Using pituitary magnetic resonance imaging for diagnosis of cavernous or sphenoid sinus invasion, immunocytochemistry, markers of the cell cycle (Ki-67, mitoses) and p53, tumours were classified according to size (micro, macro and giant), type (PRL, GH, FSH/LH, ACTH and TSH) and grade (grade 1a: non-invasive, 1b: non-invasive and proliferative, 2a: invasive, 2b: invasive and proliferative, and 3: metastatic). The association between patient status at 8-year follow-up and age, sex, and classification was evaluated by two multivariate analyses assessing disease- or recurrence/progression-free status. At 8 years after surgery, 195 patients were disease-free (controls) and 215 patients were not (cases). In 125 of the cases the tumours had recurred or progressed. Analyses of disease-free and recurrence/progression-free status revealed the significant prognostic value (p

Published
2013

61. Cholangiocarcinoma stem-like subset shapes tumor-initiating niche by educating associated macrophages

Author

Raggi, C, Correnti, M, Sica, A, Andersen, J, Cardinale, V, Alvaro, D, Chiorino, G, Forti, E, Glaser, S, Alpini, G, Destro, A, Sozio, F, Di Tommaso, L, Roncalli, M, Banales, J, Coulouarn, C, Bujanda, L, Torzilli, G, Invernizzi, P, INVERNIZZI, PIETRO, Raggi, C, Correnti, M, Sica, A, Andersen, J, Cardinale, V, Alvaro, D, Chiorino, G, Forti, E, Glaser, S, Alpini, G, Destro, A, Sozio, F, Di Tommaso, L, Roncalli, M, Banales, J, Coulouarn, C, Bujanda, L, Torzilli, G, Invernizzi, P, and INVERNIZZI, PIETRO

Abstract

Background & Aims A therapeutically challenging subset of cells, termed cancer stem cells (CSCs) are responsible for cholangiocarcinoma (CCA) clinical severity. Presence of tumor-associated macrophages (TAMs) has prognostic significance in CCA and other malignancies. Thus, we hypothesized that CSCs may actively shape their tumor-supportive immune niche. Methods CCA cells were cultured in 3D conditions to generate spheres. CCA sphere analysis of in vivo tumorigenic-engraftment in immune-deficient mice and molecular characterization was performed. The in vitro and in vivo effect of CCA spheres on macrophage precursors was tested after culturing healthy donor cluster of differentiation (CD)14+ with CCA-sphere conditioned medium. Results CCA spheres engrafted in 100% of transplanted mice and revealed a significant 20.3-fold increase in tumor-initiating fraction (p = 0.0011) and a sustained tumorigenic potential through diverse xenograft-generations. Moreover, CCA spheres were highly enriched for CSC, liver cancer and embryonic stem cell markers both at gene and protein levels. Next, fluorescence-activated cell sorting analysis showed that in the presence of CCA sphere conditioned medium, CD14+ macrophages expressed key markers (CD68, CD115, human leukocyte antigen-D related, CD206) indicating that CCA sphere conditioned medium was a strong macrophage-activator. Gene expression profile of CCA sphere activated macrophages revealed unique molecular TAM-like features confirmed by high invasion capacity. Also, freshly isolated macrophages from CCA resections recapitulated a similar molecular phenotype of in vitro-educated macrophages. Consistent with invasive features, the largest CD163+ set was found in the tumor front of human CCA specimens (n = 23) and correlated with a high level of serum cancer antigen 19.9 (n = 17). Among mediators released by CCA spheres, only interleukin (IL)13, IL34 and osteoactivin were detected and further confirmed in CCA patient sera (n = 12). S

Published
2017

66. SIMULTANEOUS OR DELAYED EVAR FOR COMBINED THORACIC AND ABDOMINAL AORTIC ANEURYSM

Author

DI TOMMASO L, MONACO M, CORONELLA G, LA MARCA GIORDANO A, PISCIONE F, STASSANO P, MAINENTI P. P., IANNELLI, GABRIELE, Di Tommaso, L., Iannelli, G., Monaco, M., Coronella, G., La Marca Giordano, A., Piscione, F., Stassano, P., Mainenti, P., DI TOMMASO, L, Iannelli, Gabriele, Monaco, M, Coronella, G, LA MARCA GIORDANO, A, Piscione, F, Stassano, P, and Mainenti, P. P.

Published
2005

72. Quantitation of the RANK-RANKL axis in primary biliary cholangitis

Author

Lleo, A, Bian, Z, Zhang, H, Miao, Q, Yang, F, Peng, Y, Chen, X, Tang, R, Wang, Q, Qiu, D, Fang, J, Sobacchi, C, Villa, A, Di Tommaso, L, Roncalli, M, Gershwin, M, Ma, X, Invernizzi, P, INVERNIZZI, PIETRO, Lleo, A, Bian, Z, Zhang, H, Miao, Q, Yang, F, Peng, Y, Chen, X, Tang, R, Wang, Q, Qiu, D, Fang, J, Sobacchi, C, Villa, A, Di Tommaso, L, Roncalli, M, Gershwin, M, Ma, X, Invernizzi, P, and INVERNIZZI, PIETRO

Abstract

There is substantial data that suggests an abnormality of innate immunity in patients with primary biliary cholangitis (PBC) which includes the transcription factor nuclear factor-kB (NF-kB) and well as downstream inflammatory signaling pathways. In addition, Immuno-Chip analysis has identified a novel PBC-associated locus near the receptor activator of NF-kB ligand (RANKL) gene. Based on these observations, we investigated the role of the RANKL axis in the liver of patients with PBC compared to controls. We used immunohistochemistry to quantitate liver expression of RANKL, its receptor (RANK), and importantly the decoy receptor osteoprotegerin (OPG), including a total of 122 liver samples (PBC = 37, primary sclerosing cholangitis = 20, autoimmune hepatitis = 26, chronic hepatitis B = 32 and unaffected controls = 7). In addition, we studied RANKL-RANK-OPG co-localization in CD4 and CD8 T cells, B cells, dendritic cells, macrophages, NK, NKT cells, hepatocytes, and cholangiocytes. We report herein that RANK is constitutively expressed by cholangiocytes in both unaffected and diseased liver. However, cholangiocytes from PBC express significantly higher levers of RANK than either the unaffected controls or liver diseased controls. CD4, CD8 and CD19 cells with in the portal areas around bile ducts in PBC express significantly higher levels of RANKL compared to controls. Importantly, the overall hepatic RANKL level and the ratio of hepatic RANKL/OPG correlated with disease severity in PBC. In conclusion, our data indicate a role of RANK-RANKL axis in the innate immune activation in PBC and we hypothesize that the damaged cholangiocytes, which express high levels of RANK, lead to the recruitment of RANKL positive cells and ultimately the classic portal tract infiltrates.

Published
2016

73. An immune stratification reveals a subset of PD-1/LAG-3 double-positive triple-negative breast cancers

Author

Bottai, G, Raschioni, C, Losurdo, A, Di Tommaso, L, Tinterri, C, Torrisi, R, Reis-Filho, JS, Roncalli, M, Sotiriou, C, Santoro, A, Mantovani, A, Loi, S, Santarpia, L, Bottai, G, Raschioni, C, Losurdo, A, Di Tommaso, L, Tinterri, C, Torrisi, R, Reis-Filho, JS, Roncalli, M, Sotiriou, C, Santoro, A, Mantovani, A, Loi, S, and Santarpia, L

Abstract

BACKGROUND: Stromal tumor-infiltrating lymphocytes (TILs) are a robust prognostic factor in triple-negative breast cancer (TNBC). However, the clinical significance of TILs may be influenced by the complex landscape of the tumor immune microenvironment. In this study, we aimed to evaluate the composition and the functionality of lymphocytic infiltration and checkpoint receptors in TNBC. METHODS: Formalin-fixed, paraffin-embedded tissues were retrospectively collected from a cohort of patients with early-stage TNBC treated with adjuvant anthracycline-based chemotherapy (n = 259). Results were validated in an independent cohort of patients with TNBC (n = 104). Stromal TILs were evaluated on hematoxylin-and-eosin-stained sections. The density of CD4+, CD8+, and FOXP3+ lymphocytes, and the expression of the immune checkpoints PD-1 and LAG-3, were assessed by immunohistochemical analysis. RESULTS: The presence of elevated TILs positively correlated with the density of all T cell subtypes, especially cytotoxic CD8+ lymphocytes. We showed that increasing stromal TILs assessed as a continuous variable is an independent prognostic marker of prolonged relapse-free survival and overall survival in TNBC. Among immune subpopulations, CD8+ lymphocytes are the main effectors of anti-tumor immune responses. In two independent cohorts, we found that PD-1 and LAG-3 were concurrently expressed in approximately 15% of patients with TNBC. The expression of both checkpoint receptors positively correlated with the presence of TILs, but was not significantly associated with patient outcome. CONCLUSIONS: Overall, our data indicate that the evaluation of stromal TILs remains the most reliable immune prognostic marker in TNBC, and support the clinical evaluation of anti-PD-1/PD-L1 and anti-LAG-3 in a subset of patients with TNBC who have concurrent expression of both checkpoint receptors.

Published
2016

83. HER2 positive breast cancer with central nervous system metastases: Pathological features and clinical outcome

Author

Masci, G., primary, Santarpia, L., additional, Bottai, G., additional, Giordano, L., additional, Zuradelli, M., additional, Torrisi, R., additional, Di Tommaso, L., additional, Sagona, A., additional, Errico, V., additional, Gatzemeier, W., additional, Testori, A., additional, Navarria, P., additional, Bello, L., additional, Tinterri, C., additional, Scorsetti, M., additional, and Santoro, A., additional

Published
2016
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87. Cholangiocarcinoma Stem-Like Subset Shapes Tumor-Initiating Niche by Educating Associated Macrophages

Author

Raggi, C., primary, Correnti, M., additional, Sica, A., additional, Andersen, J.B., additional, Cardinale, V., additional, Alvaro, D., additional, Chiorino, G., additional, Glaser, S.G., additional, Alpini, G., additional, Sozio, F., additional, Di Tommaso, L., additional, Roncalli, M., additional, Torzilli, G., additional, and Invernizzi, P., additional

Published
2016
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88. ENDOVASCULAR STENT-GRAFT REPAIR OF TRAUMATIC AORTIC RUPTURE

Author

IANNELLI, GABRIELE, DI TOMMASO L., MONACO M., TECCHIA L. B., PASSANNANTI T., SARNO G., PISCIONE F., SMIMMO R., Iannelli, Gabriele, DI TOMMASO, L., Monaco, M., Tecchia, L. B., Passannanti, T., Sarno, G., Piscione, F., and Smimmo, R.

Published
2005

91. THORACIC AORTIC DISEASE:IMPACT OF ENDOVASCULAR SURGERY

Author

DI TOMMASO L, MONACO M, MAINENTI P. P, CONTALDO A, ADURNO G, SARNO G, PISCIONE F., IANNELLI, GABRIELE, DI TOMMASO, L, Iannelli, Gabriele, Monaco, M, MAINENTI P., P, Contaldo, A, Adurno, G, Sarno, G, and Piscione, F.

Published
2005

93. ENDOVASCULAR SURGERY FOR THORACIC AORTIC PATHOLOGY

Author

IANNELLI, GABRIELE, MONACO M., DI TOMMASO L., MOTTOLA M., PINNA G., DE AMICIS, VINCENZO, SARNO G., PISCIONE F., Iannelli, Gabriele, Monaco, M., DI TOMMASO, L., Mottola, M., Pinna, G., DE AMICIS, Vincenzo, Sarno, G., and Piscione, F.

Published
2005

94. MicroRNA-425-3p predicts response to sorafenib therapy in patients with hepatocellular carcinoma

Author

Vaira, V, Roncalli, M, Carnaghi, C, Faversani, A, Maggioni, M, Augello, C, Rimassa, L, Pressiani, T, Spagnuolo, G, Di Tommaso, L, Fagiuoli, S, Rota Caremoli, E, Barberis, M, Labianca, R, Santoro, A, Bosari, S, Bosari, S., SPAGNUOLO, GAIA, Vaira, V, Roncalli, M, Carnaghi, C, Faversani, A, Maggioni, M, Augello, C, Rimassa, L, Pressiani, T, Spagnuolo, G, Di Tommaso, L, Fagiuoli, S, Rota Caremoli, E, Barberis, M, Labianca, R, Santoro, A, Bosari, S, Bosari, S., and SPAGNUOLO, GAIA

Abstract

Background & Aims: Sorafenib is the standard of care in advanced hepatocellular carcinoma (HCC), however no criteria have been established to select patients likely to benefit from this therapy. In this study, we evaluated the predictive role of microRNAs (miRNAs) in this setting of patients. Methods: We profiled 522 miRNA in a series of 26 HCC patients treated with sorafenib (training set) and validated the results in an independent series of 58 patients (validation set). Formalin-fixed paraffin-embedded tumour and cirrhotic liver biopsies were used for RNA extraction and miRNAs profiling with TaqMan Arrays technology. Statistical analyses were used to correlate miRNA levels with clinical outcome, including time to progression (TTP), progression free (PFS), and overall survival. Cell viability and cell motility of HuH-7 or HepG2 HCC cells were tested in vitro after transfection with specific miRNA precursor, inhibitor or controls and sorafenib treatment. Results: Six miRNAs were significantly associated with clinical variables in the training set and only miR-425-3p could be further validated. Higher levels of miR-425-3p were associated with longer TTP and PFS (P = 0.0008; HR = 0.4; 95% CI = 0.2-0.7 and P = 0.007; HR = 0.5; 95% CI = 0.3-0.9 respectively). Multivariate analysis confirmed the predictive significance of miR-425-3p. Furthermore, an association between increased miR-425-3p, cell death and reduced cell motility was defined in vitro in HCC cell lines treated with sorafenib. Conclusions: Assessment of miR-425-3p levels in liver biopsies could help in stratifying patients with advanced HCC for sorafenib treatment. These promising results need to be confirmed in a large prospective study.

Published
2015

95. Ultrafiltrazione e ultradiafiltrazione continua con controllo volumetrico automatizzato nel trattamento dell'insufficienza renale postoperatoria: esperienza in 36 pazienti

Author

MUSUMECI, ANTONINO, MANNACIO, VITO ANTONIO, GAGLIARDI, CESARE, DE AMICIS, VINCENZO, Di Tommaso, L, Caputo, M, Spampinato, N., Musumeci A, Di Tommaso L, Caputo M, Mannacio V, Gagliardi C, De Amicis V, Spampinato N., Musumeci, Antonino, Di Tommaso, L, Caputo, M, Mannacio, VITO ANTONIO, Gagliardi, Cesare, DE AMICIS, Vincenzo, and Spampinato, N.

Published
1995

96. Advantages of endovascular AAA repair in elderly patients at very high surgical risk

Author

Sarno G, and Piscione F, and Iannelli G, and Accardo D, and Viola O, and Di Tommaso L, and Monaco M, and Chiariello M, G., Sarno, F., Piscione, Iannelli, Gabriele, D., Accardo, O., Viola, L. D., Tommaso, M., Monaco, M., Chiariello, Sarno, G, and Piscione, F, and Iannelli, G, and Accardo, D, and Viola, O, and Di Tommaso, L, and Monaco, M, and and Chiariello, M

Published
2004

97. ACUTE TYPE-B AORTIC DISSECTION:IMPACT OF ENDOVASCULAR SURGERY

Author

TRUNFIO S., MONACO M., DI TOMMASO L., MOTTOLA M., TROISI N., BOTTA L., PISCIONE F., IANNELLI, GABRIELE, Trunfio, S., Monaco, M., DI TOMMASO, L., Mottola, M., Troisi, N., Botta, L., Piscione, F., and Iannelli, Gabriele

Published
2004

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