المؤلفون: Colli, Maikel L., Hill, Jessica L. E., Marroquí, Laura, Chaffey, Jessica, Dos Santos, Reinaldo S., Leete, Pia, Coomans de Brachène, Alexandra, Paula, Flavia M. M., Op de Beeck, Anne, Castela, Angela, Marselli, Lorella, Krogvold, Lars, Dahl-Jorgensen, Knut, Marchetti, Piero, Morgan, Noel G., Richardson, Sarah J., Eizirik, Décio L.

المساهمون: Colli, Maikel L., Hill, Jessica L. E., Marroquí, Laura, Chaffey, Jessica, Dos Santos, Reinaldo S., Leete, Pia, Coomans de Brachène, Alexandra, Paula, Flavia M. M., Op de Beeck, Anne, Castela, Angela, Marselli, Lorella, Krogvold, Lar, Dahl-Jorgensen, Knut, Marchetti, Piero, Morgan, Noel G., Richardson, Sarah J., Eizirik, Décio L.

مصطلحات موضوعية: CD274, Immune checkpoint inhibitor, IRF1, Pancreatic beta cell, Pancreatic islet, PDL-1, PDL1, Type 1 diabete, Adolescent, Adult, B7-H1 Antigen, Biomarker, Cell Line, Child, Preschool, Diabetes Mellitus, Type 1, Human, Insulin-Secreting Cell, Interferon Regulatory Factor-1, Interferon-alpha, Interferon-gamma, Islets of Langerhan, Middle Aged, Young Adult, Gene Expression Regulation, Biochemistry, Genetics and Molecular Biology (all)

الوصف: Background: Antibodies targeting PD-1 and its ligand PDL1 are used in cancer immunotherapy but may lead to autoimmune diseases, including type 1 diabetes (T1D). It remains unclear whether PDL1 is expressed in pancreatic islets of people with T1D and how is it regulated. Methods: The expression of PDL1, IRF1, insulin and glucagon was evaluated in samples of T1D donors by immunofluorescence. Cytokine-induced PDL1 expression in the human beta cell line, EndoC-βH1, and in primary human pancreatic islets was determined by real-time RT-PCR, flow cytometry and Western blot. Specific and previously validated small interference RNAs were used to inhibit STAT1, STAT2, IRF1 and JAK1 signaling. Key results were validated using the JAK inhibitor Ruxolitinib. Findings: PDL1 was present in insulin-positive cells from twelve T1D individuals (6 living and 6 deceased donors) but absent from insulin-deficient islets or from the islets of six non-diabetic controls. Interferons-α and -γ, but not interleukin-1β, induced PDL1 expression in vitro in human islet cells and EndoC-βH1 cells. Silencing of STAT1 or STAT2 individually did not prevent interferon-α-induced PDL1, while blocking of JAKs – a proposed therapeutic strategy for T1D – or IRF1 prevented PDL1 induction. Interpretation: These findings indicate that PDL1 is expressed in beta cells from people with T1D, possibly to attenuate the autoimmune assault, and that it is induced by both type I and II interferons via IRF1.

وصف الملف: ELETTRONICO

العلاقة: info:eu-repo/semantics/altIdentifier/pmid/30269996; info:eu-repo/semantics/altIdentifier/wos/WOS:000447685300041; volume:36; firstpage:367; lastpage:375; numberofpages:9; journal:EBIOMEDICINE; info:eu-repo/grantAgreement/EC/H2020/115797 667191; http://hdl.handle.net/11568/954955Test; info:eu-repo/semantics/altIdentifier/scopus/2-s2.0-85054193057; https://www.sciencedirect.com/science/article/pii/S2352396418303980Test

الإتاحة: https://doi.org/10.1016/j.ebiom.2018.09.040Test
http://hdl.handle.net/11568/954955Test
https://www.sciencedirect.com/science/article/pii/S2352396418303980Test

المؤلفون: Neri M., Frati A., Turillazzi E., Cantatore S., Cipolloni L., Di Paolo M., Frati P., La Russa R., Maiese A., Scopetti M., Santurro A., Sessa F., Zamparese R., Fineschi V.

المساهمون: Neri, M., Frati, A., Turillazzi, E., Cantatore, S., Cipolloni, L., Di Paolo, M., Frati, P., La Russa, R., Maiese, A., Scopetti, M., Santurro, A., Sessa, F., Zamparese, R., Fineschi, V.

مصطلحات موضوعية: Aquaporin, Computed tomography (CT) scan, Edema, Genetic analysi, Hypoxia, Microglia activation, Traumatic brain injury, Adult, Aged, Antigens, CD, Differentiation, Myelomonocytic, Aquaporin 4, Base Sequence, Brain Edema, Brain Injuries, Traumatic, Calcium-Binding Protein, DNA-Binding Protein, Female, Glial Fibrillary Acidic Protein, Human, Hypoxia-Inducible Factor 1, alpha Subunit, Immunohistochemistry, Lewis X Antigen, Male, Microfilament Protein, Middle Aged

الوصف: Traumatic brain injury (TBI) is one of the leading causes of death and disability worldwide. Our understanding of its pathobiology has substantially increased. Following TBI, the following occur, edema formation, brain swelling, increased intracranial pressure, changes in cerebral blood flow, hypoxia, neuroinflammation, oxidative stress, excitotoxicity, and apoptosis. Experimental animal models have been developed. However, the difficulty in mimicking human TBI explains why few neuroprotective strategies, drawn up on the basis of experimental studies, have translated into improved therapeutic strategies for TBI patients. In this study, we retrospectively examined brain samples in 145 cases of death after different survival times following TBI, to investigate aquaporin-4 (AQP4) expression and correlation with hypoxia, and neuroinflammation in human TBI. Antibodies anti-glial fibrillary acid protein (GFAP), aquaporin-4 (AQP4), hypoxia induced factor-1α (HIF-1α), macrophage/phagocytic activation (CD68), ionized calcium-binding adapter molecule-1 (IBA-1), and neutrophils (CD15) were used. AQP4 showed a significant, progressive increase between the control group and groups 2 (one-day survival) and 3 (three-day survival). There were further increases in AQP4 immunopositivity in groups 4 (seven-day survival), 5 (14-dayssurvival), and 6 (30-day survival), suggesting an upregulation of AQP4 at 7 to 30 days compared to group 1. GFAP showed its highest expression in non-acute cases at the astrocytic level compared with the acute TBI group. Data emerging from the HIF-1α reaction showed a progressive, significant increase. Immunohistochemistry with IBA-1 revealed activated microglia starting three days after trauma and progressively increasing in the next 15 to 20 days after the initial trauma. CD68 expression demonstrated basal macrophage and phagocytic activation mostly around blood vessels. Starting from one to three days of survival after TBI, an increase in the number of CD68 cells was progressively observed; at 15 and ...

وصف الملف: ELETTRONICO

العلاقة: info:eu-repo/semantics/altIdentifier/pmid/30423808; info:eu-repo/semantics/altIdentifier/wos/WOS:000451528500260; volume:19; issue:11; firstpage:3544; journal:INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES; http://hdl.handle.net/11568/1067007Test; info:eu-repo/semantics/altIdentifier/scopus/2-s2.0-85056543279

الإتاحة: https://doi.org/10.3390/ijms19113544Test
http://hdl.handle.net/11568/1067007Test

المؤلفون: D'Addio F., Maestroni A., Assi E., Ben Nasr M., Amabile G., Usuelli V., Loretelli C., Bertuzzi F., Antonioli B., Cardarelli F., El Essawy B., Solini A., Gerling I. C., Bianchi C., Becchi G., Mazzucchelli S., Corradi D., Fadini G. P., Foschi D., Markmann J. F., Orsi E., Skrha J., Camboni M. G., Abdi R., James Shapiro A. M., Folli F., Ludvigsson J., Del Prato S., Zuccotti G., Fiorina P.

المساهمون: D'Addio, F., Maestroni, A., Assi, E., Ben Nasr, M., Amabile, G., Usuelli, V., Loretelli, C., Bertuzzi, F., Antonioli, B., Cardarelli, F., El Essawy, B., Solini, A., Gerling, I. C., Bianchi, C., Becchi, G., Mazzucchelli, S., Corradi, D., Fadini, G. P., Foschi, D., Markmann, J. F., Orsi, E., Skrha, J., Camboni, M. G., Abdi, R., James Shapiro, A. M., Folli, F., Ludvigsson, J., Del Prato, S., Zuccotti, G., Fiorina, P.

مصطلحات موضوعية: Adult, Animal, Cells, Cultured, Diabetes Mellitus, Type 1, Type 2, Female, Homeostasi, Human, Immunoblotting, Insulin-Like Growth Factor Binding Protein 3, Insulin-Secreting Cell, Male, Membrane Protein, Mice, Inbred C57BL, Inbred NOD, Knockout, Transgenic, Middle Aged, Reverse Transcriptase Polymerase Chain Reaction, Signal Transduction, Gene Expression Regulation

الوصف: Loss of pancreatic beta cells is a central feature of type 1 (T1D) and type 2 (T2D) diabetes, but a therapeutic strategy to preserve beta cell mass remains to be established. Here we show that the death receptor TMEM219 is expressed on pancreatic beta cells and that signaling through its ligand insulin-like growth factor binding protein 3 (IGFBP3) leads to beta cell loss and dysfunction. Increased peripheral IGFBP3 was observed in established and at-risk T1D/T2D patients and was confirmed in T1D/T2D preclinical models, suggesting that dysfunctional IGFBP3/TMEM219 signaling is associated with abnormalities in beta cells homeostasis. In vitro and in vivo short-term IGFBP3/TMEM219 inhibition and TMEM219 genetic ablation preserved beta cells and prevented/delayed diabetes onset, while long-term IGFBP3/TMEM219 blockade allowed for beta cell expansion. Interestingly, in several patients’ cohorts restoration of appropriate IGFBP3 levels was associated with improved beta cell function. The IGFBP3/TMEM219 pathway is thus shown to be a physiological regulator of beta cell homeostasis and is also demonstrated to be disrupted in T1D/T2D. IGFBP3/TMEM219 targeting may therefore serve as a therapeutic option in diabetes.

وصف الملف: ELETTRONICO

العلاقة: info:eu-repo/semantics/altIdentifier/pmid/35115561; info:eu-repo/semantics/altIdentifier/wos/WOS:000752207900013; volume:13; issue:1; firstpage:684; journal:NATURE COMMUNICATIONS; http://hdl.handle.net/11568/1136917Test; info:eu-repo/semantics/altIdentifier/scopus/2-s2.0-85124057555

الإتاحة: https://doi.org/10.1038/s41467-022-28360-2Test
http://hdl.handle.net/11568/1136917Test

المؤلفون: Girolami, Ilaria, Mancini, Irene, Simoni, Antonella, Baldi, Giacomo Giulio, Simi, Lisa, Campanacci, Domenico, Beltrami, Giovanni, Scoccianti, Guido, D'Arienzo, Antonio, CAPANNA, RODOLFO, FRANCHI, ALESSANDRO

المساهمون: Girolami, Ilaria, Mancini, Irene, Simoni, Antonella, Baldi, Giacomo Giulio, Simi, Lisa, Campanacci, Domenico, Beltrami, Giovanni, Scoccianti, Guido, D'Arienzo, Antonio, Capanna, Rodolfo, Franchi, Alessandro

مصطلحات موضوعية: BONE TUMOURS, CANCER GENETICS, IMMUNOCYTOCHEMISTRY, Adolescent, Adult, Aged, Angiogenesis Inhibitor, Bone Density Conservation Agent, Bone Neoplasm, Cell Proliferation, Core Binding Factor Alpha 1 Subunit, Denosumab, Female, Giant Cell Tumor of Bone, Histone, Human, Male, Matrix Attachment Region Binding Protein, Middle Aged, Mutation, Neovascularization, Pathologic, Predictive Value of Test, RANK Ligand, Receptor Activator of Nuclear Factor-kappa B, Transcription Factor, Treatment Outcome, Young Adult, Biomarkers, Tumor

الوقت: 2734

الوصف: Aims: Denosumab, a fully human monoclonal antibody directed against RANKL, has recently been introduced in the treatment strategy of giant cell tumour of bone (GCTB). Aim of this study was to investigate the phenotypical modifications induced by denosumab treatment in a series of 15 GCTB. Methods: The tumours were characterised for histone 3.3 mutations, and studied immunohistochemically for the modifications of RANKL, RANK, SATB2 and RUNX2 expression, as well as of tumour proliferative activity and angiogenesis. Results: Nine of 11 tumours investigated presented a histone 3.3 mutation in H3F3A, and 2 of these for which the analysis was carried out in pretreatment and post-treatment specimens showed the same mutation in both. Denosumab induced the disappearance of osteoclast-like giant cells, leaving residual spindle neoplastic cells arranged in a storiform pattern, with deposition of trabecular collagen matrix and osteoid, which tended to maturation in the peripheral portions of the lesion. RANK and RANKL expression was variable, with no significant variation after treatment. Moreover, we did not observe any significant modification of the expression of the osteoblastic markers SATB2 and RUNX2. Denosumab treatment determined a significant reduction of the proliferative index and of tumour angiogenesis (p=0.001, Wilcoxon rank-sum test). Conclusions: These results indicate that denosumab induces a partial maturation towards the osteoblastic phenotype of the neoplastic cells of GCTB, with production of fibrous and osteoid matrix, but with minor immunophenotypical changes. Finally, we first report an antiangiogenic activity of denosumab in GCTB, possibly mediated by a RANKL-dependent pathway.

العلاقة: info:eu-repo/semantics/altIdentifier/pmid/26338802; info:eu-repo/semantics/altIdentifier/wos/WOS:000370829100008; volume:69; issue:3; firstpage:240; lastpage:247; numberofpages:8; journal:JOURNAL OF CLINICAL PATHOLOGY; http://hdl.handle.net/11568/804508Test; info:eu-repo/semantics/altIdentifier/scopus/2-s2.0-84959345838; https://jcp.bmj.com/content/69/3/240lTest

الإتاحة: https://doi.org/10.1136/jclinpath-2015-203248Test
http://hdl.handle.net/11568/804508Test
https://jcp.bmj.com/content/69/3/240lTest

المؤلفون: Pi-Sunyer, Xavier, Astrup, Arne, Fujioka, Ken, Greenway, Frank, Halpern, Alfredo, Krempf, Michel, Lau, David C. W., le Roux, Carel W., Ortiz, Violante, Jensen, Christine Bjorn, Wilding, John P. H., Hamann A, Barakat A, Blüher M, Linn T, DALLE MOLLE, ALBERTO, Segner A, Stübler P, Tosch-Sisting R, Pacini F, Santini F, Marchesini G, Rotella CM, Invitti C, Vettor R, Buscemi S, Raya PM, Freijoo FC, de Barbará RG, Carraro R, Bobillo ER, de la Cuesta C, Farsang C, Csaszar A, Zahorska-Markiewicz B, Pupek-Musialik D, Franek E, Ostrowska L, Olszanecka-Glinianowicz M, Lalic N, Micic D, Ludvik B, Paulweber B, Prager R, Scheen A, Van Gaal L, Astrup AV, Hermansen K, Madsbad S, Rissanen A, Nieminen S, Savolainen M, Krempf M, Romon M, Laville M, Marre M, Mira R, Finucane F, Veenendaal A, van Berkum F, Johannsson-Vidarsdóttir S, Van de Walle V, Meesters E, Hjelmesæth J, Klemsdal TO, Kulseng B, Bach-Kliegel B, Laederach K, Villiger L, Golay A, Bilz S, Sathyapalan T, Bain S, Kumar S, Le Roux CW, Lean ME, McGowan B, Rehman T, Wilding J, Wittert G, Caterson I, Proietto J, Prins J, Geloneze Neto B, Gross JL, Chacra AR, Halpern A, Suplicy Hde A, Chow FC, Thacker HP, Chadha M, Chandalia H, Unnikrishnan A, Kalra S, Deshpande N, Shunmugavelu M, Deshmukh VC, Maislos M, Lieberman GS, Shimon I, Stern N, Nabriski D, Karnieli E, Shehadeh N, Gonzalez-Galvez G, Arechavaleta-Granell Mdel R, Violante Ortiz RM, Franco GM, Gurieva I, Suplotova LA, Troshina E, Ruyatkina LA, Voychik EA, Martsevich S, Startseva MA, Seeber ME, Badat A, Ellis G, Altuntas Y, Guler S, Ulgen E, Delibasi T, Chetty T, Hart R, Janzen J, Labonte I, Lau D, Liutkus J, O'Keefe D, Padwal R, Ransom TP, Tytus R, Weisnagel SJ, Adler J, Aqua K, Aronoff SL, Bedel GW, Blevins TC, Blumenau J, Brockmyre AP, Call RS, Canadas R, Chaykin LB, Cohen K, Conrow JK, Davis MG, Downey HJ, Drosman SR, Duckor S, Farmer H, Farrell J, Fehnel S, Finneran MP, Forbes R, Forker A, Fredrick M, Fujioka K, Geller SA, Gill S, Glaser L, Greco SN, Greenway FL, Harper W, Herman L, Hoekstra J, Ingebretsen R, Ison R, Jain RK, Kaplan R, Kaster SR, Haase GA, Kerzner B, Kirstein JL, Koltun W, Krieger DR, Lewis CE, Madder R, Marple RN, McDermott EJ, Mello CJ, Miller AB, Mullen J, Nardandrea J, O'Neil P, Pi-Sunyer F, Pucillo RM, Rhee C, Redrick S, Pardini A, Rothman J, Rubino DM, Sellers G, Smith T, Byars WD, Soufer J, Sussman AM, Patrick K, Schramm EL, Van Cleeff M, Berg SR, Wyatt HR, Simon JA.

المساهمون: Pi-Sunyer, Xavier, Astrup, Arne, Fujioka, Ken, Greenway, Frank, Halpern, Alfredo, Krempf, Michel, Lau, David C. W., le Roux, Carel W., Ortiz, Violante, Jensen, Christine Bjorn, Wilding, John P. H., Hamann, A, Barakat, A, Blüher, M, Linn, T, DALLE MOLLE, Alberto, Segner, A, Stübler, P, Tosch-Sisting, R, Pacini, F, Santini, F, Marchesini, G, Rotella, Cm, Invitti, C, Vettor, R, Buscemi, S, Raya, Pm, Freijoo, Fc, de Barbará, Rg, Carraro, R, Bobillo, Er, de la Cuesta, C, Farsang, C, Csaszar, A, Zahorska-Markiewicz, B, Pupek-Musialik, D, Franek, E, Ostrowska, L, Olszanecka-Glinianowicz, M, Lalic, N, Micic, D, Ludvik, B, Paulweber, B, Prager, R, Scheen, A, Van Gaal, L, Astrup, Av, Hermansen, K, Madsbad, S, Rissanen, A, Nieminen, S, Savolainen, M, Krempf, M, Romon, M, Laville, M, Marre, M, Mira, R, Finucane, F, Veenendaal, A, van Berkum, F, Johannsson-Vidarsdóttir, S, Van de Walle, V, Meesters, E, Hjelmesæth, J, Klemsdal, To, Kulseng, B, Bach-Kliegel, B, Laederach, K, Villiger, L, Golay, A, Bilz, S, Sathyapalan, T, Bain, S, Kumar, S, Le Roux, Cw, Lean, Me, Mcgowan, B, Rehman, T, Wilding, J, Wittert, G, Caterson, I, Proietto, J, Prins, J, Geloneze Neto, B, Gross, Jl, Chacra, Ar, Halpern, A, Suplicy Hde, A, Chow, Fc, Thacker, Hp, Chadha, M, Chandalia, H, Unnikrishnan, A, Kalra, S, Deshpande, N, Shunmugavelu, M, Deshmukh, Vc, Maislos, M, Lieberman, G, Shimon, I

مصطلحات موضوعية: Adult, Blood Glucose, Body Mass Index, Combined Modality Therapy, Counseling, Diarrhea, Diet, Reducing, Double-Blind Method, Exercise, Female, Glucagon-Like Peptide 1, Human, Hypoglycemic Agent, Injections, Subcutaneou, Liraglutide, Male, Middle Aged, Nausea, Obesity, Weight Lo, Medicine (all)

الوصف: BACKGROUND Obesity is a chronic disease with serious health consequences, but weight loss is difficult to maintain through lifestyle intervention alone. Liraglutide, a glucagonlike peptide-1 analogue, has been shown to have potential benefit for weight management at a once-daily dose of 3.0 mg, injected subcutaneously. METHODS We conducted a 56-week, double-blind trial involving 3731 patients who did not have type 2 diabetes and who had a body-mass index (BMI; the weight in kilograms divided by the square of the height in meters) of at least 30 or a BMI of at least 27 if they had treated or untreated dyslipidemia or hypertension. We randomly assigned patients in a 2:1 ratio to receive once-daily subcutaneous injections of liraglutide at a dose of 3.0 mg (2487 patients) or placebo (1244 patients); both groups received counseling on lifestyle modification. The coprimary end points were the change in body weight and the proportions of patients losing at least 5% and more than 10% of their initial body weight. RESULTS At baseline, the mean (±SD) age of the patients was 45.1±12.0 years, the mean weight was 106.2±21.4 kg, and the mean BMI was 38.3±6.4; a total of 78.5% of the patients were women and 61.2% had prediabetes. At week 56, patients in the liraglutide group had lost a mean of 8.4±7.3 kg of body weight, and those in the placebo group had lost a mean of 2.8±6.5 kg (a difference of -5.6 kg; 95% confidence interval, -6.0 to -5.1; P<0.001, with last-observation-carried-forward imputation). A total of 63.2% of the patients in the liraglutide group as compared with 27.1% in the placebo group lost at least 5% of their body weight (P<0.001), and 33.1% and 10.6%, respectively, lost more than 10% of their body weight (P<0.001). The most frequently reported adverse events with liraglutide were mild or moderate nausea and diarrhea. Serious events occurred in 6.2% of the patients in the liraglutide group and in 5.0% of the patients in the placebo group. CONCLUSIONS In this study, 3.0 mg of liraglutide, as an ...

وصف الملف: ELETTRONICO

العلاقة: info:eu-repo/semantics/altIdentifier/pmid/26132939; info:eu-repo/semantics/altIdentifier/wos/WOS:000357218700004; volume:373; issue:1; firstpage:11; lastpage:22; numberofpages:12; journal:NEW ENGLAND JOURNAL OF MEDICINE; http://hdl.handle.net/11568/855260Test; info:eu-repo/semantics/altIdentifier/scopus/2-s2.0-84936166069

الإتاحة: https://doi.org/10.1056/NEJMoa1411892Test
http://hdl.handle.net/11568/855260Test

المؤلفون: Ottaviano M., Curvietto M., Rescigno P., Tortora M., Palmieri G., Giannarelli D., Aieta M., Assalone P., Attademo L., Avallone A., Bloise F., Bosso D., Borzillo V., Buono G., Calderoni G., Caputo F., Carteni G., Cavallero D., Cavo A., Ciardiello F., Conca R., Conteduca V., De Falco S., De Felice M., De Laurentiis M., De Placido P., De Placido S., De Santo I., De Stefano A., Della Corte C. M., Di Franco R., Di Lauro V., Fabbrocini A., Federico P., Festino L., Giordano P., Giuliano M., Gridelli C., Grimaldi A. M., Lia M., Marretta A. L., Massa V., Mennitto A., Merler S., Merz V., Messina C., Messina M., Milano M., Minisini A. M., Montesarchio V., Morabito A., Morgillo F., Mucci B., Nappi L., Napolitano F., Paciolla I., Pagliuca M., Parola S., Pepe S., Petrillo A., Piantedosi F., Piccin L., Picozzi F., Pietroluongo E., Pignata S., Prati V., Riccio V., Rosanova M., Rossi A., Russo A., Salati M., Santabarbara G., Sbrana A., Simeone E., Silvestri A., Spada M., Tarantino P., Taveggia P., Tomei F., Vincenzo T., Trapani D., Trojanello C., Vanella V., Vari S., Ventriglia J., Vitale M. G., Vitiello F., Vivaldi C., Von Arx C., Zacchi F., Zampiva I., Zivi A., Daniele B., Ascierto P. A.

المساهمون: Ottaviano, M., Curvietto, M., Rescigno, P., Tortora, M., Palmieri, G., Giannarelli, D., Aieta, M., Assalone, P., Attademo, L., Avallone, A., Bloise, F., Bosso, D., Borzillo, V., Buono, G., Calderoni, G., Caputo, F., Carteni, G., Cavallero, D., Cavo, A., Ciardiello, F., Conca, R., Conteduca, V., De Falco, S., De Felice, M., De Laurentiis, M., De Placido, P., De Placido, S., De Santo, I., De Stefano, A., Della Corte, C. M., Di Franco, R., Di Lauro, V., Fabbrocini, A., Federico, P., Festino, L., Giordano, P., Giuliano, M., Gridelli, C., Grimaldi, A. M., Lia, M., Marretta, A. L., Massa, V., Mennitto, A., Merler, S., Merz, V., Messina, C., Messina, M., Milano, M., Minisini, A. M., Montesarchio, V., Morabito, A., Morgillo, F., Mucci, B., Nappi, L., Napolitano, F., Paciolla, I., Pagliuca, M., Parola, S., Pepe, S., Petrillo, A., Piantedosi, F., Piccin, L., Picozzi, F., Pietroluongo, E., Pignata, S., Prati, V., Riccio, V., Rosanova, M., Rossi, A., Russo, A., Salati, M., Santabarbara, G., Sbrana, A., Simeone, E., Silvestri, A., Spada, M., Tarantino, P., Taveggia, P., Tomei, F., Vincenzo, T., Trapani, D., Trojanello, C., Vanella, V., Vari, S., Ventriglia, J., Vitale, M. G., Vitiello, F., Vivaldi, C., Von Arx, C., Zacchi, F., Zampiva, I., Zivi, A., Daniele, B., Ascierto, P. A.

مصطلحات موضوعية: antineoplastic protocol, healthcare economics and organization, immunotherapy, lung neoplasm, melanoma, Adult, Antineoplastic Agents, Immunological, B7-H1 Antigen, Betacoronaviru, COVID-19, CTLA-4 Antigen, Coronavirus Infection, Drug Prescription, Female, Geography, Human, Infection Control, Italy, Male, Medical Oncology, Neoplasm, Oncologist, Pandemic, Pneumonia, Viral, Practice Patterns, Physicians', Prevalence, Programmed Cell Death 1 Receptor

الوصف: Background The coronavirus disease 2019 (COVID-19) pandemic has overwhelmed the health systems worldwide. Data regarding the impact of COVID-19 on cancer patients (CPs) undergoing or candidate for immune checkpoint inhibitors (ICIs) are lacking. We depicted the practice and adaptations in the management of patients with solid tumors eligible or receiving ICIs during the COVID-19 pandemic, with a special focus on Campania region. Methods This survey (25 questions), promoted by the young section of SCITO (Società Campana di ImmunoTerapia Oncologica) Group, was circulated among Italian young oncologists practicing in regions variously affected by the pandemic: high (group 1), medium (group 2) and low (group 3) prevalence of SARS-CoV-2-positive patients. For Campania region, the physician responders were split into those working in cancer centers (CC), university hospitals (UH) and general hospitals (GH). Percentages of agreement, among High (H) versus Medium (M) and versus Low (L) group for Italy and among CC, UH and GH for Campania region, were compared by using Fisher's exact tests for dichotomous answers and χ 2 test for trends relative to the questions with 3 or more options. Results This is the first Italian study to investigate the COVID-19 impact on cancer immunotherapy, unique in its type and very clear in the results. The COVID-19 pandemic seemed not to affect the standard practice in the prescription and delivery of ICIs in Italy. Telemedicine was widely used. There was high consensus to interrupt immunotherapy in SARS-CoV-2-positive patients and to adopt ICIs with longer schedule interval. The majority of the responders tended not to delay the start of ICIs; there were no changes in supportive treatments, but some of the physicians opted for delaying surgeries (if part of patients' planned treatment approach). The results from responders in Campania did not differ significantly from the national ones. Conclusion Our study highlights the efforts of Italian oncologists to maintain high standards of care ...

العلاقة: info:eu-repo/semantics/altIdentifier/pmid/33060148; info:eu-repo/semantics/altIdentifier/wos/WOS:000583157800005; volume:8; issue:2; firstpage:e001154; journal:JOURNAL FOR IMMUNOTHERAPY OF CANCER; http://hdl.handle.net/11568/1114478Test; info:eu-repo/semantics/altIdentifier/scopus/2-s2.0-85093476336

الإتاحة: https://doi.org/10.1136/jitc-2020-001154Test
http://hdl.handle.net/11568/1114478Test

المؤلفون: Lupi, Isabella, Brancatella, Alessandro, Cosottini, Mirco, Viola, Nicola, Lanzolla, Giulia, Sgrò, Daniele, Dalmazi, Giulia Di, Latrofa, Francesco, Caturegli, Patrizio, Marcocci, Claudio

المساهمون: Lupi, Isabella, Brancatella, Alessandro, Cosottini, Mirco, Viola, Nicola, Lanzolla, Giulia, Sgrò, Daniele, Dalmazi, Giulia Di, Latrofa, Francesco, Caturegli, Patrizio, Marcocci, Claudio

مصطلحات موضوعية: ACTH, Adenocarcinoma, Adult, Asthenia, Atezolizumab, Autoimmune disorder, Autoimmune hypophysiti, CT scan, Cortisol, Diabetes mellitus type 1, Diabetic ketoacidosi, FSH, Fatigue, Female, Fludrocortisone, Glucocorticoid, Glucose (blood), Gonadotrophin, Gonadotropin, HLA genotyping, Headache, Hydrocortisone, Hyperglycaemia, Hypergonadotropic hypogonadism, Hyperkalaemia, Hypoadrenalism, Hypogonadism, Hyponatraemia, Hypophysiti

الوقت: 2019

الوصف: Programmed cell death protein 1/programmed cell death protein ligand 1 (PD-1/PD-L1) and cytotoxic T-lymphocyte antigen 4/B7 (CTLA-4/B7) pathways are key regulators in T-cell activation and tolerance. Nivolumab, pembrolizumab (PD-1 inhibitors), atezolizumab (PD-L1 inhibitor) and ipilimumab (CTLA-4 inhibitor) are monoclonal antibodies approved for treatment of several advanced cancers. Immune checkpoint inhibitors (ICIs)-related hypophysitis is described more frequently in patients treated with anti-CTLA-4; however, recent studies reported an increasing prevalence of anti-PD-1/PD-L1-induced hypophysitis which also exhibits slightly different clinical features. We report our experience on hypophysitis induced by anti-PD-1/anti-PD-L1 treatment. We present four cases, diagnosed in the past 12 months, of hypophysitis occurring in two patients receiving anti-PD-1, in one patient receiving anti-PD-1 and anti-CTLA-4 combined therapy and in one patient receiving anti-PD-L1. In this case series, timing, clinical presentation and association with other immune-related adverse events appeared to be extremely variable; central hypoadrenalism and hyponatremia were constantly detected although sellar magnetic resonance imaging did not reveal specific signs of pituitary inflammation. These differences highlight the complexity of ICI-related hypophysitis and the existence of different mechanisms of action leading to heterogeneity of clinical presentation in patients receiving immunotherapy.

العلاقة: info:eu-repo/semantics/altIdentifier/pmid/31610523; info:eu-repo/semantics/altIdentifier/wos/WOS:000489783300001; volume:2019; journal:ENDOCRINOLOGY, DIABETES & METABOLISM CASE REPORTS; http://hdl.handle.net/11568/1017035Test; info:eu-repo/semantics/altIdentifier/scopus/2-s2.0-85076233658

الإتاحة: https://doi.org/10.1530/EDM-19-0102Test
http://hdl.handle.net/11568/1017035Test

المؤلفون: Santaguida, Maria Giulia, Gatto, Ilenia, Mangino, Giorgio, Virili, Camilla, Stramazzo, Ilaria, Fallahi, Poupak, Antonelli, Alessandro, Segni, Maria, Romeo, Giovanna, Centanni, Marco

المساهمون: Santaguida, Maria Giulia, Gatto, Ilenia, Mangino, Giorgio, Virili, Camilla, Stramazzo, Ilaria, Fallahi, Poupak, Antonelli, Alessandro, Segni, Maria, Romeo, Giovanna, Centanni, Marco

مصطلحات موضوعية: Breg cell, Cellular immunity, Hashimoto's thyroiditi, Polyglandular autoimmune syndrome, Thyroid autoimmunity, ADP-ribosyl Cyclase 1, Adult, Antigens, CD19, Autoimmune Disease, B-Lymphocytes, Regulatory, CD24 Antigen, Case-Control Studie, Celiac Disease, Female, Gastritis, Atrophic, Hashimoto Disease, Human, Interleukin-10, Male, Membrane Glycoprotein, Middle Aged, Th17 Cell, Tumor Necrosis Factor Receptor Superfamily, Member 7, Vitiligo, Immunology and Allergy, Immunology

الوصف: Hashimoto thyroiditis (HT) may occur isolated or associated with other non-endocrine autoimmune disorders (NEAD). No data are available about Breg cells in these disorders and this represented the aim of the study. Th17 and Breg cells subset were characterized on peripheral blood mononuclear cells isolated from 18 healthy donors (HD), 19 patients with isolated HT and 26 patients with HT + NEAD. Th17 were higher in patients with isolated HT than in HD but no further changes were seen in patients with HT + NEAD. CD24hiCD38hiunstimulated Breg cells were similar in HT patients and in HD, but significantly higher in patients with HT + NEAD than in both HT and in HD. CD19+CD24hiCD27+Breg memory phenotype was similar in HD and in HT patients, but decreased in patients with HT + NEAD (23.4%vs38.5%). Upon CpG-stimulation, CD24hiCD38hiIL-10+Breg cells were higher in HT patients than in HD (3.9%vs1.8%) but similar in patients with HT + NEAD (2.4%).

العلاقة: info:eu-repo/semantics/altIdentifier/pmid/28461108; info:eu-repo/semantics/altIdentifier/wos/WOS:000414888300005; volume:184; firstpage:42; lastpage:47; numberofpages:6; journal:CLINICAL IMMUNOLOGY; http://hdl.handle.net/11568/920367Test; info:eu-repo/semantics/altIdentifier/scopus/2-s2.0-85018985338; https://www.sciencedirect.com/science/article/pii/S152166161630568XTest

الإتاحة: https://doi.org/10.1016/j.clim.2017.04.012Test
http://hdl.handle.net/11568/920367Test
https://www.sciencedirect.com/science/article/pii/S152166161630568XTest

المؤلفون: CRISCI, ISABELLA, Aragona, Michele, Politi, Konstantina Savvina, DANIELE, GIUSEPPE, DEL PRATO, STEFANO

المساهمون: Crisci, Isabella, Aragona, Michele, Politi, Konstantina Savvina, Daniele, Giuseppe, DEL PRATO, Stefano

مصطلحات موضوعية: Continuous glucose monitoring, Glycemic variability, Insulin pump therapy, Liraglutide, Type 1 diabete, Adult, Aged, Area Under Curve, Blood Glucose, Body Mass Index, C-Peptide, Diabetes Mellitus, Type 1, Female, Glucagon-Like Peptide-1 Receptor, Hemoglobin A, Glycosylated, Human, Hypoglycemia, Hypoglycemic Agent, Male, Middle Aged, Endocrinology, Internal Medicine, Diabetes and Metabolism

الوصف: Aims: To test potential efficacy of liraglutide, a GLP-1 receptor agonist, in subjects with type 1 diabetes (T1DM). Methods: We have recruited nine T1DM patients (age 40.1±6.4years, duration of diabetes 19.2±8.8years, BMI 24.3±3.5kg/m2, HbA1c 8.2±1.0%–66±11mmol/mol, daily insulin dose: 0.6±0.1IU/kg) on continuous subcutaneous insulin therapy with undetectable C-peptide. In addition to existing treatment was administered in single-blind (a) therapy subcutaneously with 0.1ml of saline solution for 3days and (b) 0.1ml of liraglutide (0.6mg/day) for a further 3days with daily glucose excursions recorded by continuous glucose monitoring. Results: Adding liraglutide resulted in a significant reduction in mean blood glucose (138±29 vs. 163±29mg/dl, p<0.0001) and standard deviation (42±9 vs. 60±15mg/dl, p<0.0001). The area under the curve (AUC) for blood glucose >140mg/dl was also significantly reduced (22.2±16.4 vs. 41.1±19.7mg/dlh, p<0.05) with no difference in AUC for blood glucose <70mg/dl (liraglutide 0.7±0.9mg/dlh; placebo: 0.8±1.4mg/dlh, p=NS). Finally, adding liraglutide reduced daily insulin requirement (37.5±17.2 vs. 42.9±22.4 UI/day, p<0.01). Conclusions: Short-term treatment with liraglutide, in T1DM, reduces average blood glucose, blood glucose variability and daily insulin requirement without increasing risk of hypoglycemia.

وصف الملف: STAMPA

العلاقة: info:eu-repo/semantics/altIdentifier/pmid/26293127; info:eu-repo/semantics/altIdentifier/wos/WOS:000363950500014; volume:52; issue:6; firstpage:1129; lastpage:1133; numberofpages:5; journal:ACTA DIABETOLOGICA; http://hdl.handle.net/11568/763653Test; info:eu-repo/semantics/altIdentifier/scopus/2-s2.0-84945461146; link.springer.de/link/service/journals/00592/index.htm

الإتاحة: https://doi.org/10.1007/s00592-015-0800-6Test
http://hdl.handle.net/11568/763653Test

المؤلفون: Peeters, Stijn A., Engelen, Lian, Buijs, Jacqueline, Chaturvedi, Nish, Fuller, John H., Schalkwijk, Casper G., Stehouwer, Coen D, Karamanos, B., Kofinis, A., Petrou, K., Giorgino, F., Picca, G., Angarano, A., Null, de P.e.r.g.o.l.a. G., Laviola, L., Giorgino, R., Ionescu Tirgoviste, C., Coszma, A., Guja, C., Songini, M., Casu, A., Pedron, M., Pintus, S., Fossarello, M., Ferriss, J. B., Grealy, G., O'Keefe, D., Toeller, M., Arden, C., Rottiers, R., Tuyttens, C., Priem, H., Ebeling, P., Kylliainen, M., Koivisto, V. A., Idzior Walus, B., Sieradzki, J., Cyganek, K., Solnica, B., Lemkes, H. H. P. J., Lemkes Stuffken, J. C., Nunes Correa, J., Rogado, M. C., Gardete Correia, L., Cardoso, M. C., Silva, A., Boavida, J., Machado Sa Marques, M., Michel, G., Wirion, R., Cardillo, S., Pozza, G., Mangili, R., Asnaghi, V., Standl, E., Schaffler, B., Brand, H., Harms, A., Ben Soussan, M., Verier Mine, O., Fallas, P., Fallas, M. C., Fuller, J. H., Holloway, J., Asbury, L., Betteridge, D. J., Cathelineau, G., Bouallouche, A., Villatte Cathelineau, B., Santeusanio, F., Rosi, G., D'Alessandro, V., Cagini, C., Bottini, P., Reboldi, G. P., Navalesi, R., Bandinelli, S., Ghirlanda, G., Saponara, C., Cotroneo, P., Manto, A., Minnella, A., Ward, J. D., Tesfaye, S., Eaton, S., Mody, C., Borra, M., Cavallo Perin, P., Giunti, S., Grassi, G., Pagano, G. F., Porta, M., Sivieri, R., Vitelli, F., Veglio, M., Papazoglou, N., Manes, G., Muggeo, M., Iagulli, M., Cacciatori, V., Cattedra di Malattie del Metabolismo, V., Irsigler, K., Abrahamian, H., Walford, S., Sinclair, J., Hughes, S., Mclelland, V., Ward, J., Roglic, G., Metelko, Z., Pepeonik, Z. R., PENNO, GIUSEPPE, MICCOLI, ROBERTO, NANNIPIERI, MONICA

المساهمون: Peeters, Stijn A., Engelen, Lian, Buijs, Jacqueline, Chaturvedi, Nish, Fuller, John H., Schalkwijk, Casper G., Stehouwer, Coen D, Karamanos, B., Kofinis, A., Petrou, K., Giorgino, F., Picca, G., Angarano, A., Null, de P. e. r. g. o. l. a. G., Laviola, L., Giorgino, R., Ionescu Tirgoviste, C., Coszma, A., Guja, C., Songini, M., Casu, A., Pedron, M., Pintus, S., Fossarello, M., Ferriss, J. B., Grealy, G., O'Keefe, D., Toeller, M., Arden, C., Rottiers, R., Tuyttens, C., Priem, H., Ebeling, P., Kylliainen, M., Koivisto, V. A., Idzior Walus, B., Sieradzki, J., Cyganek, K., Solnica, B., Lemkes, H. H. P. J., Lemkes Stuffken, J. C., Nunes Correa, J., Rogado, M. C., Gardete Correia, L., Cardoso, M. C., Silva, A., Boavida, J., Machado Sa Marques, M., Michel, G., Wirion, R., Cardillo, S., Pozza, G., Mangili, R., Asnaghi, V., Standl, E., Schaffler, B., Brand, H., Harms, A., Ben Soussan, M., Verier Mine, O., Fallas, P., Fallas, M. C., Fuller, J. H., Holloway, J., Asbury, L., Betteridge, D. J., Cathelineau, G., Bouallouche, A., Villatte Cathelineau, B., Santeusanio, F., Rosi, G., D'Alessandro, V., Cagini, C., Bottini, P., Reboldi, G. P., Navalesi, R., Penno, Giuseppe, Bandinelli, S., Miccoli, Roberto, Nannipieri, Monica, Ghirlanda, G., Saponara, C., Cotroneo, P., Manto, A., Minnella, A., Ward, J. D., Tesfaye, S., Eaton, S., Mody, C., Borra, M., Cavallo Perin, P., Giunti, S., Grassi, G., Pagano, G. F., Porta, M., Sivieri, R., Vitelli, F., Veglio, M., Papazoglou, N., Manes, G.

مصطلحات موضوعية: Albuminuria, Cardiovascular disease, Matrix metalloproteinase, Retinopathy, Tissue inhibitor of metalloproteinase, Type 1 diabete, Adult, Biomarker, Cohort Studie, Cross-Sectional Studie, Diabetes Complication, Diabetes Mellitus, Type 1, Europe, Female, Human, Male, Matrix Metalloproteinase 10, Matrix Metalloproteinase 2, Matrix Metalloproteinase 3, Middle Aged, Prospective Studie, Tissue Inhibitor of Metalloproteinase-1, Vascular Disease, Endocrinology, Diabetes and Metabolism, Cardiology and Cardiovascular Medicine

الوصف: Impaired regulation of extracellular matrix remodeling by matrix metalloproteinases (MMPs) and tissue inhibitor of metalloproteinase (TIMP) may contribute to vascular complications in patients with type 1 diabetes. We investigated associations between plasma MMP-1, -2, -3, -9, -10 and TIMP-1, and cardiovascular disease (CVD) or microvascular complications in type 1 diabetic patients. We also evaluated to which extent these associations could be explained by low-grade inflammation (LGI) or endothelial dysfunction (ED). Methods: 493 type 1 diabetes patients (39.5 ± 9.9 years old, 51% men) from the EURODIAB Prospective Complications Study were included. Linear regression analysis was applied to investigate differences in plasma levels of MMP-1, -2, -3, -9, -10, and TIMP-1 between patients with and without CVD, albuminuria or retinopathy. All analyses were adjusted for age, sex, duration of diabetes, Hba1c and additionally for other cardiovascular risk factors including LGI and ED. Results: Patients with CVD (n = 118) showed significantly higher levels of TIMP-1 [β = 0.32 SD (95%CI: 0.12; 0.52)], but not of MMPs, than patients without CVD (n = 375). Higher plasma levels of MMP-2, MMP-3, MMP-10 and TIMP-1 were associated with higher levels of albuminuria (p-trends were 0.028, 0.004, 0.005 and 0.001, respectively). Severity of retinopathy was significantly associated with higher levels of MMP-2 (p-trend = 0.017). These associations remained significant after further adjustment for markers of LGI and ED. Conclusions: These data support the hypothesis that impaired regulation of matrix remodeling by actions of MMP-2, -3 and-10 and TIMP-1 contributes to the pathogenesis of vascular complications in type 1 diabetes.

وصف الملف: STAMPA

العلاقة: info:eu-repo/semantics/altIdentifier/pmid/25848912; volume:14; issue:1; firstpage:31; journal:CARDIOVASCULAR DIABETOLOGY; http://hdl.handle.net/11568/838374Test; info:eu-repo/semantics/altIdentifier/scopus/2-s2.0-84925234995; http://www.cardiab.com/homeTest/

الإتاحة: https://doi.org/10.1186/s12933-015-0195-2Test
http://hdl.handle.net/11568/838374Test
http://www.cardiab.com/homeTest/