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5. Association of a CT-based clinical and radiomics score of non-small cell lung cancer (NSCLC) with lymph node status and overall survival

Author

Botta, F, Raimondi, S, Rinaldi, L, Bellerba, F, Corso, F, Bagnardi, V, Origgi, D, Minelli, R, Pitoni, G, Petrella, F, Spaggiari, L, Morganti, A, del Grande, F, Bellomi, M, Rizzo, S, Botta F., Raimondi S., Rinaldi L., Bellerba F., Corso F., Bagnardi V., Origgi D., Minelli R., Pitoni G., Petrella F., Spaggiari L., Morganti A. G., del Grande F., Bellomi M., Rizzo S., Botta, F, Raimondi, S, Rinaldi, L, Bellerba, F, Corso, F, Bagnardi, V, Origgi, D, Minelli, R, Pitoni, G, Petrella, F, Spaggiari, L, Morganti, A, del Grande, F, Bellomi, M, Rizzo, S, Botta F., Raimondi S., Rinaldi L., Bellerba F., Corso F., Bagnardi V., Origgi D., Minelli R., Pitoni G., Petrella F., Spaggiari L., Morganti A. G., del Grande F., Bellomi M., and Rizzo S.

Abstract

Background: To evaluate whether a model based on radiomic and clinical features may be associated with lymph node (LN) status and overall survival (OS) in lung cancer (LC) patients; to evaluate whether CT reconstruction algorithms may influence the model performance. Methods: patients operated on for LC with a pathological stage up to T3N1 were retrospectively selected and divided into training and validation sets. For the prediction of positive LNs and OS, the Least Absolute Shrinkage and Selection Operator (LASSO) logistic regression model was used; univariable and multivariable logistic regression analysis assessed the association of clinicalradiomic variables and endpoints. All tests were repeated after dividing the groups according to the CT reconstruction algorithm. p-values < 0.05 were considered significant. Results: 270 patients were included and divided into training (n = 180) and validation sets (n = 90). Transfissural extension was significantly associated with positive LNs. For OS prediction, high-and low-risk groups were different according to the radiomics score, also after dividing the two groups according to reconstruction algorithms. Conclusions: a combined clinical–radiomics model was not superior to a single clinical or single radiomics model to predict positive LNs. A radiomics model was able to separate high-risk and low-risk patients for OS; CTs reconstructed with Iterative Reconstructions (IR) algorithm showed the best model performance.

Published
2020

13. p53 Is a Master Regulator of Proteostasis in SMARCB1-Deficient Malignant Rhabdoid Tumors

Author

Carugo, A., Minelli, R., Sapio, L., Soeung, M., Carbone, F., Robinson, F. S., Tepper, J., Chen, Z., Lovisa, S., Svelto, M., Amin, S., Srinivasan, S., Del Poggetto, E., Loponte, S., Puca, F., Dey, P., Malouf, G. G., Su, X., Li, L., Lopez-Terrada, D., Rakheja, D., Lazar, A. J., Netto, G. J., Rao, P., Sgambato, A., Maitra, A., Tripathi, D. N., Walker, C. L., Karam, J. A., Heffernan, T. P., Viale, A., Roberts, C. W. M., Msaouel, P., Tannir, N. M., Draetta, G. F., Genovese, G., Sgambato A. (ORCID:0000-0002-9487-4563), Genovese G., Carugo, A., Minelli, R., Sapio, L., Soeung, M., Carbone, F., Robinson, F. S., Tepper, J., Chen, Z., Lovisa, S., Svelto, M., Amin, S., Srinivasan, S., Del Poggetto, E., Loponte, S., Puca, F., Dey, P., Malouf, G. G., Su, X., Li, L., Lopez-Terrada, D., Rakheja, D., Lazar, A. J., Netto, G. J., Rao, P., Sgambato, A., Maitra, A., Tripathi, D. N., Walker, C. L., Karam, J. A., Heffernan, T. P., Viale, A., Roberts, C. W. M., Msaouel, P., Tannir, N. M., Draetta, G. F., Genovese, G., Sgambato A. (ORCID:0000-0002-9487-4563), and Genovese G.

Abstract

Alterations in chromatin remodeling genes have been increasingly implicated in human oncogenesis. Specifically, the biallelic inactivation of the SWI/SNF subunit SMARCB1 results in the emergence of extremely aggressive pediatric malignancies. Here, we developed embryonic mosaic mouse models of malignant rhabdoid tumors (MRTs) that faithfully recapitulate the clinical-pathological features of the human disease. We demonstrated that SMARCB1-deficient malignancies exhibit dramatic activation of the unfolded protein response (UPR) and ER stress response via a genetically intact MYC-p19 ARF -p53 axis. As a consequence, these tumors display an exquisite sensitivity to agents inducing proteotoxic stress and inhibition of the autophagic machinery. In conclusion, our findings provide a rationale for drug repositioning trials investigating combinations of agents targeting the UPR and autophagy in SMARCB1-deficient MRTs.

Published
2019

16. Abstracts of the XVIII European Conference on Muscle and Motility: De Blije Werelt, Lunteren, The Netherlands September 12–16, 1989

Author

Nesterov, V. P., Peiper, U., Hiller, J., Krienke, B., Schüttler, K., Szymanski, C., Bottinelli, R., Cappelli, V., Minelli, R., Reggiani, C., Schiaffino, S., Carlhoff, D., D'Haese, J., Dabrowska, R., Nowak, E., Borovikov, Y. S., Cummins, P., Russell, G., McLoughlin, D., Cummins, B., Bonet, A., Harricane, M. C., Audemard, E., Mornet, D., Ropert, S., Cavaillé, F., Redwood, C. S., Bryan, J., Cross, R. A., Kendrick-Jones, J., Marston, S. B., Taggart, M., Marston, S., Makuch, R., Stokarska, G., Dabrowska, R., Cecchi, G., Colomo, F., Poggesi, C., Tesi, C., Puceat, M., Clement, O., Lechene, P., Pelosin, J. -M., Ventura-Clapter, R., Vassort, G., Fischer, W., Pfitzer, G., Ankrett, R. J., Rowe, A. J., Bagshaw, C. R., Perry, S. V., Hebisch, S., Levine, B., Moir, A. J. G., Leszyk, J., Derancourt, J., Patcheil, V., Cavadore, C., Collins, J. H., Swiderek, K., Jaquet, K., Mittmann, K., Meyer, H. E., Heilmeyer, Jr, L. M. J., Travers, F., Barman, T., Duvert, M., Grandier-Vazeille, X., Verna, A., Dan-Goor, M., Mühlrad, A., Muhlrad, A., Polzar, B., Kießling, P., Mannherz, H. G., Lehmann-Klose, S., Gröschel-Stewart, U., Bettache, N., Bertrand, R., Kassab, R., Roulet, A., Cardinaud, R., Harford, J. J., Squire, J. M., Maeda, Y., Chew, M. W. K., Huber, Pia, Schaub, Marcus C., Pierobon-Bormioli, S., Betto, R., Ceoldo, S., Salviati, G., Martinez, I., Ofstad, R., Olsen, R. L., Trinick, J., Barlow, D., Gautel, M., Gibson, T., Labeit, S., Leonard, K., Wardale, J., Whiting, A., Draeger, A., Barth, M., Herzog, M., Gimona, M., Small, J. V., Stelzer, E., Amos, B., Ikebe, M., Bernengo, J. C., Rinne, Bettina, Wray, John S., Poole, K. J. V., Goody, R. S., Thomas, Daniel, Rowe, Arthur, Schröder, R. R., Hofmann, W., Müller, U. C., Menetret, J. -F., Wray, J. S., Lakey, A., Tichelaar, W., Ferguson, C., Bullard, B., Kabsch, W., Pai, E. F., Suck, D., Holmes, K. C., Jarosch, Robert, van Mastrigt, R., Pollack, Gerald H., Horowitz, Arie, Anderl, R., Kuhn, H. J., Burton, K., Jung, D. W. G., Blangé, T., Treijtel, B. W., Bagni, M. A., Garzella, P., Huxley, A. F., Beckers-Bleukx, G., Maréchal, G., Bershitsky, S. Y., Tsaturyan, A. K., Woodward, S. K. A., Eccleston, J. F., Geeves, M. A., Knight, Peter, Fortune, Neil, Geeves, Mike, Arner, A., Arheden, H., Lombardi, V., Piazzesi, G., Stienen, G. J. M., Elzinga, G., de Beer, E. L., van Buuren, K. J. H., ten Kate, Y. J., Grundeman, R. L. F., Schiereck, P., Trombitas, K., Versteeg, P. G. A., Rowe, Arthur J., Bolger, Paul, van der Laarse, W. J., Diegenbach, P. C., Flitney, F. W., Jones, D. A., Hatfaludy, S., Shansky, J., Smiley, B., Vandenburgh, H. H., de Haan, A., Lodder, M. A. N., Berquin, A., Lebacq, J., Curtin, N. A., Woledge, R. C., Hellstrand, P., Lönnbro, P., Wadsö, I., Lammertse, T. S., Zaremba, R., Daut, J., Woledge, R. C., Kushmerick, M. J., McFarland, E., Lyons, G. E., Sassoon, D., Ontell, M., and Buckingham, M. E.

Published
1990
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22. THE ITALIAN MASTOCYTOSIS REGISTRY: THE FIRST FIVE YEARS

Author

Merante, S., Neri, I., Magliacane, D., Fortina, A. Belloni, Ingeborg, F., Pastorello, E. A., Mauro, M., Minelli, R., Difonzo, E. D. Elisa, Guggiari, E., Peserico, A., Romani, I., Bocchia, M., Fontana, E., Di Nuzzo, S., Elli, E. M., Elena, C., Virginia Valeria Ferretti, Brazzelli, V., Ciccocioppo, R., Di Stefano, M., Bossi, G., Boveri, E., Virdi, A., and Triggiani, M.

Published
2015

36. 4-Hydroxynonenal, a lipid peroxidation product of dietary polyunsaturated fatty acids, has anticarcinogenic properties in colon carcinoma cell lines through the inhibition of telomerase activity

Author

Pizzimenti S. 1, Menegatti E. 2, Berardi D. 2, Toaldo C. 1, Pettazzoni P. 1, Minelli R. 1, Giglioni B. 3, Cerbone A. 1, Dianzani M.U. 1, Ferretti C. 4, and Barrera G. 1

Subjects
4-Hydroxynonenal, Caco-2, hTERT gene expression, GSH, HT-29, Telomerase activity, Myc/Mad/Max network
Abstract

The effects of polyunsaturated fatty acids (PUFAs) obtained from the diet on colorectal cancer have been widely explored. However, controversial results have been obtained about the role played by the lipid peroxidation products of PUFAs, such as 4-hydroxy-nonenal (HNE), in the control of colon cancer growth. This aldehyde, indeed, showed both procarcinogenic and protective effects. In an attempt to verify the action of HNE, we studied the effects of a low dose of HNE (1 muM), similar to those "physiologically" found in normal cells and plasma, on telomerase activity, a key parameter of malignant transformation. Caco-2 cells were exposed to HNE and, paralleling cell growth inhibition, we observed the down-regulation of telomerase activity and hTERT expression. Similar effects have also been observed in HT-29 cells, in which HNE inhibited cell proliferation, telomerase activity and hTERT expression, suggesting that the inhibition of telomerase activity could be a general mechanism involved in the antiproliferative effect exerted by this aldehyde. Finally, we elucidated the mechanism of hTERT inhibition by HNE. A reduction of GSH content preceded the decrease of telomerase activity, but this only partially explained the telomerase activity inhibition. The major mechanism of HNE action seems to be the modulation of expression and activity of transcription factors belonging to the Myc/Mad/Max network. Since the presence of PUFAs in the diet exposes epithelial colon cells to HNE, this aldehyde could contribute to cell growth control through the inhibitory action on telomerase activity and hTERT expression, suggesting a protective effect on colon mucosa.

Published
2010

37. Viticultural zoning of Valtellina (Northern Italy)

Author

Murada, G., Failla, O., Mariani, L., Minelli, R., and Scienza, A.

Subjects
Viticulture, Land suitability, Zoning, Settore AGR/03 - Arboricoltura Generale e Coltivazioni Arboree
Published
2006

44. Lack of increased serum interleukin-6 and soluble IL-6 receptor concentrations in patients with thyroid diseases following recombinant human interferon alpha therapy

Author

Minelli R, Girasole G, Pedrazzoni M, Nicola Giuliani, Schianchi C, Giuberti T, Le, Braverman, Salvi M, and Roti E

Subjects
Male, Thyrotoxicosis, Antigens, CD, Interleukin-6, Humans, Interferon-alpha, Female, Receptors, Interleukin, Hyperthyroidism, Receptors, Interleukin-6, Thyroid Diseases, Recombinant Proteins, Hepatitis, Chronic
Abstract

Serum interleukin-6 (IL-6) concentrations are frequently elevated in inflammatory thyroid diseases, such as subacute thyroiditis and amiodarone induced thyroiditis. We and others have recently observed that recombinant interferon-alpha (rIFN-alpha) therapy for chronic, active viral hepatitis and malignant disorders may induce thyroid dysfunction, including thyrotoxicosis secondary to thyroiditis. Serum IL-6 and its soluble receptor (sIL-6R) have been measured for the first time in patients with chronic active hepatitis receiving rIFN-alpha therapy.Studies were carried out in 37 patients treated with rIFN-alpha for chronic, active viral hepatitis. Thyroid function tests and serum IL-6 and sIL-6R were measured before and during rIFN-alpha therapy.Six patients developed inflammatory or destructive thyrotoxicosis confirmed by elevated serum free T4 or free T3 concentrations, suppressed serum thyroid-stimulating hormone (TSH) values, and a low thyroid radioactive iodine uptake. Serum IL-6 and sIL-6R concentrations were not elevated in these patients with rIFN-alpha-induced thyroiditis.These results suggest that serum IL-6 concentrations are not useful in differentiating between inflammatory thyrotoxicosis and hyperthyroidism induced by rIFN-alpha therapy as is the case in amiodarone-induced thyrotoxicosis. It is possible that rIFN-alpha therapy could be associated with an inhibitory effect of rIFN-alpha on the release of IL-6 from damaged thyroid cells and not on the basal secretion of IL-6.

Published
1996

47. Can misdiagnosis in pre-operative FNAC of thyroid nodule influence surgical treatment?

Author

Rio, P., Minelli, R., Cataldo, S., Ceresini, G., Robuschi, G., Corcione, L., Guazzi, A., Nizzoli, R., and Sianesi, M.

Abstract

Background: Pre-operative cytology in thyroid disease remains the most appropriate diagnostic test for defining the nature of a thyroid nodule before surgical excision. Materials and methods: We selected the most recent 825 surgical thyroid procedures performed in our institution from January 2004 to June 2007; 776 were total thyroidectomies, 23 were lobe-isthmectomies, and 26 were radical neck dissections. We distributed the data based on pre-operative cytology. Each cytological diagnosis was compared to results obtained by definitive histology. Tumors were called incidentalomas if they consisted of a neoplastic focus with a low grade of aggressiveness, as demonstrated by dimension <5 mm, non-aggressive histological subtype. Results: Of the 541 cases of benign disease, 417 were confirmed as benign. The other 124 cases are listed as follows: 29 follicular adenoma; 76 papillary carcinoma (35 found as incidentalomas), and 19 follicular carcinoma (3 incidentalomas). Cytology suggestive of papillary carcinoma was correct in 95.2% of cases (119/125). The 135 tumors termed “follicular neoplasm” were staged on pathology thus: 56 adenoma (41.4%), 26 carcinoma (19.2%), 13 (9.6%) absence of follicular proliferation, 38 (28.1%) papillary follicular variant, 2 (1.4%) undifferentiated cells. Medullary carcinomas were both confirmed. The “suspicious group” exhibited no malignancy on fine needle aspiration cytology (12 of 21; 57%). Conclusions: Cytology has good reliability in malignant lesions. Incidental tumors occurring in benign disease have little impact on clinical and surgical management; “follicular neoplasm” posed two problems — the impossibility of identifying the nature of the tumor, as well as the newer difficulty in distinguishing papillary follicular subtype.

Published
2011
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48. Is Steroid Therapy Needed in the Treatment of Destructive Thyrotoxicosis Induced by α-Interferon in Chronic Hepatitis C?

Author

Minelli, R., Valli, M.A., Seclì, C. Di, Finardi, L., Chiodera, P., Bertoni, R., Ferrari, C., Barilli, A.L., Coiro, V., Jotti, G. Saccani, and Delsignore, R.

Abstract

AbstractObjective: Treatment with interferon (IFN) of patients affected by chronic hepatitis C (CH-C) may produce alterations in thyroid function, such as hypothyroidism, Graves’-like hyperthyroidism and destructive thyrotoxicosis (DT). IFN-induced DT is characterized by suppressed serum TSH levels, normal or elevated FT4 and FT3 concentrations, with the presence or absence of thyroid peroxidase antibodies and antithyroglobulin antibodies, the absence of thyroid receptor antibodies and radioactive iodine uptake suppressed or &lt;5%. Design: IFN-induced DT is a mild clinical disease, because thyroid-destructive processes last for a short time and involve a small portion of the gland. At present, the therapeutic approach in DT suggests IFN withdrawal and 1–2 months of methylprednisolone treatment. Methods: In consideration of possible untoward side effects of steroid treatment in patients with CH-C, we studied two groups of patients with CH-C who developed DT after treatments with various preparations of recombinant IFN (with or without ribavirin). Patients sequentially entered the study during a 4-year period, at the time of DT diagnosis, when IFN therapy was discontinued. The first 12 subjects (group A) were treated with 8–16 mg/day methylprednisolone for 30–40 days after IFN withdrawal; in the following 15 patients (group B), IFN withdrawal was not followed by any additional treatment. All patients underwent clinical and laboratory controls of thyroid function at 1, 2, 3 and 6 months after DT diagnosis. Results: The results showed restoration of euthyroidism in both group A and group B patients at 6 months after DT diagnosis, regardless of steroid treatment. Conclusions: The simple withdrawal of IFN therapy in patients with CH-C, who had developed DT, appears to be effective in the treatment of the thyroid disease. This therapeutic approach should be preferred in order to avoid possible undesired side effects of steroid therapy in patients with CH-C.Copyright © 2005 S. Karger AG, Basel

Published
2005

49. Serum concentrations of proinflammatory cytokines in Graves' disease: effect of treatment, thyroid function, ophthalmopathy and cigarette smoking

Author

Salvi, M, Pedrazzoni, M, Girasole, G, Giuliani, N, Minelli, R, Wall, and Roti, E

Abstract

OBJECTIVE: In the present study we have measured the concentrations of interleukin-6 (IL-6), soluble IL-6 receptor (sIL-6R), tumor necrosis factor-alpha (TNF-alpha), interleukin-1 beta (IL-1 beta) and IL-1 receptor antagonist (IL-1Ra) in the serum of patients with Graves' disease (GD). By multivariate analysis, we have evaluated the effect of antithyroid treatment, thyroid function, the presence or absence of active thyroid-associated ophthalmopathy (TAO), the patient's smoking habits and the relation to circulating anti-thyrotropin (TSH) receptor (TRAb) and anti-thyroperoxidase antibodies (TPOAb). SUBJECTS: We studied 84 GD patients, 51 untreated and 33 receiving methimazole (MMI) therapy. Twenty-three (45%) untreated patients and 18 (54%) patients on MMI had active TAO. We also studied 67 normal subjects as controls. Thirty-one GD patients (43%) and 16 controls (36%) were smokers. RESULTS: Serum IL-6 concentrations were significantly higher in both untreated patients (P<0.001) and treated patients (P<0.006), when compared with controls. Serum sIL-6R concentrations were significantly affected by treatment (P=0.001). Serum IL-1Ra concentrations were not different in GD patients, whether treated or untreated, compared with controls. Serum IL-6 concentrations were not influenced by thyroid function and there was a significant interaction between treatment and the presence of active TAO (P=0.003). In hyperthyroid patients with active TAO serum, sIL-6R concentrations were significantly higher than in those with inactive TAO (P=0.003). In untreated GD patients there was no significant effect of thyroid function and TAO activity on the serum concentrations of TNF-alpha and IL-1 beta. Serum IL-1Ra concentrations were not affected by the presence of TAO. Smoking had no effect on serum IL-6, sIL-6R, TNF-alpha, IL-1 beta and IL-1Ra concentrations, even in the presence of an active TAO. Serum concentrations of IL-6, sIL-6R, TNF-alpha and IL-1 beta and IL-1Ra were not different in patients with and without TRAb or TPOAb, in relation to either thyroid function, TAO activity or smoking. CONCLUSIONS: Our work shows that: (i) the proinflammatory cytokine pattern in GD is greatly influenced by antithyroid drug treatment; (ii) the increased circulating IL-6/sIL-6R concentrations observed in patients with active TAO may derive from the activation of humoral reactions in sites other than the thyroid; and, (iii) cigarette smoking has no effect on serum IL-1/IL-1Ra concentrations in TAO.

Published
2000

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