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2. Virtual multi-institutional tumor board: Feasibility and physicians acceptance, a GSTU foundation project in Sicily

Author

Serretta, V., primary, Scalici Gesolfo, C., additional, Gebbia, V., additional, Borsellino, N., additional, Di Trapani, D., additional, Ferrera, G., additional, Spada, M., additional, Armenio, A., additional, Lamartina, M., additional, Valerio, M.R., additional, Di Grazia, A., additional, Pennisi, M., additional, Caruso, M., additional, Ruoppolo, M., additional, Barbera, M., additional, Adamo, V., additional, Cimino, S., additional, Firenze, A., additional, Piazza, D., additional, Macchiarella, V., additional, Fazio, I., additional, and La Vecchia, M., additional

Published
2022
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4. A real benefit of an extended neonatal screening

Author

Mazzaccara C., Redi A., Albano L., Fecarotta S., Flagiello C., Crisci D., Acquaviva F., Gallo G., Nolano A., Mirra B., Pecce R., Parenti G., Villani G. R. D., Ruoppolo M., Frisso G., Mazzaccara, C., Redi, A., Albano, L., Fecarotta, S., Flagiello, C., Crisci, D., Acquaviva, F., Gallo, G., Nolano, A., Mirra, B., Pecce, R., Parenti, G., Villani, G. R. D., Ruoppolo, M., and Frisso, G.

Subjects
screening neonatale allargato, MTHFR, analisi genetica
Abstract

Methylenetetrahydrofolate Reductase (MTHFR) deficiency, is avery rare congenital defect of folate metabolism, inherited in an autosomal recessive pattern included in newbornscreening (NBS) programs in Italy. It is caused by mutations in the MTHFRgene and is characterized by elevatedplasma homocysteine and borderline-low or normal methionine levels, causing severe neurological signs, recurrentapnoea, microcephaly and convulsions, generally during the neonatal period. An early treatment may prevent theclinical manifestations with a positive impact on patient’s health. We report a new case of MTHFRdeficiency, identified during NBS that showed hypomethioninemia 4.6 μmol/L (r.i.6-20). The second level-test revealed hyperhomocysteinemia (106.7 μM, r.i. 5-15). The whole sequencing of theMTHFRgene showed two missense mutation: c.176G>C (p.Trp59Ser), reported as disease causing and the novelc.1769T>G (p.Leu590Arg), classified as likely pathogenetic. The baby was immediately treated with vitamin B12,folate and betaine; after 12 months of follow-up he has no signs or symptoms of the disease. In conclusion, this case report highlights the importance of NBS for inborn errors of metabolism and genetic analysis,that can prevent the establishment of a serious disorder of folate metabolism.

Published
2019

5. Exercise with food withdrawal at thermoneutrality impacts fuel use, the microbiome, AMPK phosphorylation, muscle fibers, and thyroid hormone levels in rats

Author

Giacco, A. (Antonia), Delli Paoli, G. (Giuseppe), Simiele, R. (Roberta), Caterino, M. (Marianna), Ruoppolo, M. (Margherita), Bloch, W. (Wilhelm), Kraaij, R. (Robert), Uitterlinden, A.G. (André G), Santillo, A. (Alessandra), Senese, R. (Rosalba), Cioffi, F. (Federica), Silvestri, E. (Elena), Iervolino, S. (Stefania), Lombardi, A. (Assunta), Moreno, M. (Maria), Goglia, F. (Fernando), Lanni, A. (Antonia), Lange, P. (Pieter) de, Giacco, A. (Antonia), Delli Paoli, G. (Giuseppe), Simiele, R. (Roberta), Caterino, M. (Marianna), Ruoppolo, M. (Margherita), Bloch, W. (Wilhelm), Kraaij, R. (Robert), Uitterlinden, A.G. (André G), Santillo, A. (Alessandra), Senese, R. (Rosalba), Cioffi, F. (Federica), Silvestri, E. (Elena), Iervolino, S. (Stefania), Lombardi, A. (Assunta), Moreno, M. (Maria), Goglia, F. (Fernando), Lanni, A. (Antonia), and Lange, P. (Pieter) de

Abstract

Exercise under fasting conditions induces a switch to lipid metabolism, eliciting beneficial metabolic effects. Knowledge of signaling responses underlying metabolic adjustments in such conditions may help to identify therapeutic strategies. Therefore, w

Published
2020
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6. Exercise with food withdrawal at thermoneutrality impacts fuel use, the microbiome, AMPK phosphorylation, muscle fibers, and thyroid hormone levels in rats

Author

Giacco, A, delli Paoli, G, Simiele, R, Caterino, M, Ruoppolo, M, Bloch, W, Kraaij, Robert, Uitterlinden, André, Santillo, A, Senese, R, Cioffi, F, Silvestri, E, Iervolino, S, Lombardi, A, Moreno, M, Goglia, F, Lanni, A, Lange, P, Giacco, A, delli Paoli, G, Simiele, R, Caterino, M, Ruoppolo, M, Bloch, W, Kraaij, Robert, Uitterlinden, André, Santillo, A, Senese, R, Cioffi, F, Silvestri, E, Iervolino, S, Lombardi, A, Moreno, M, Goglia, F, Lanni, A, and Lange, P

Published
2020

15. Rossi A, Ruoppolo M, Formisano P, Villani G, Albano L, Gallo G, Crisci D, Moccia A, Parenti G, Strisciuglio P, Melis D. Insulin-resistance in glycogen storage disease type Ia: linking carbohydrates and mitochondria? J Inherit Metab Dis. 2018 Nov;41(6):985-995. doi: 10.1007/s10545-018-0149-4. IF 4.827. Citazioni 8(Google Scholar), 7 (Scopus), 4 (ISI web of Science)

Author

Rossi, A, Ruoppolo, M, Formisano, P, Villani, G, Albano, L, Gallo, G, Crisci, D, Moccia, A, Parenti, G, Strisciuglio, P, and Melis, D.

Published
2018

18. Unravelling pathways downstream Sox6 induction in K562 erythroid cells by proteomic analysis

Author

Barbarani, G, Ronchi, A, Ruoppolo, M, Santorelli, L, Steinfelder, R, Elangovan, S, Fugazza, C, Caterino, M, Barbarani, Gloria, Ronchi, Antonella, Ruoppolo, Margherita, SANTORELLI, LUCIA, Steinfelder, Robert, Elangovan, Sudharshan, Fugazza, Cristina, Caterino, Marianna, Barbarani, G, Ronchi, A, Ruoppolo, M, Santorelli, L, Steinfelder, R, Elangovan, S, Fugazza, C, Caterino, M, Barbarani, Gloria, Ronchi, Antonella, Ruoppolo, Margherita, SANTORELLI, LUCIA, Steinfelder, Robert, Elangovan, Sudharshan, Fugazza, Cristina, and Caterino, Marianna

Abstract

The Sox6 transcription factor is crucial for terminal maturation of definitive red blood cells. Sox6-null mouse fetuses present misshapen and nucleated erythrocytes, due to impaired actin assembly and cytoskeleton stability. These defects are accompanied with a reduced survival of Sox6-/- red blood cells, resulting in a compensated anemia. Sox6-overexpression in K562 cells and in human primary ex vivo erythroid cultures enhances erythroid differentiation and leads to hemoglobinization, the hallmark of erythroid maturation. To obtain an overview on processes downstream to Sox6 expression, we performed a differential proteomic analysis on human erythroid K562 cells overexpressing Sox6. Sox6-overexpression induces dysregulation of 64 proteins, involved in cytoskeleton remodeling and in protein synthesis, folding and trafficking, key processes for erythroid maturation. Moreover, 43 out of 64 genes encoding for differentially expressed proteins contain within their proximal regulatory regions sites that are bound by SOX6 according to ENCODE ChIP-seq datasets and are possible direct SOX6 targets. SAR1B, one of the most induced proteins upon Sox6 overexpression, shares a conserved regulatory module, composed by a double SOX6 binding site and a GATA1 consensus, with the adjacent SEC24 A gene. Since both genes encode for COPII components, this element could concur to the coordinated expression of these proteins during erythropoiesis

Published
2017

19. Clinical validation of cutoff target ranges in newborn screening of metabolic disorders by tandem mass spectrometry: A worldwide collaborative project

Author

Mchugh, Dm, Cameron, Ca, Abdenur, Je, Abdulrahman, M., Adair, O., Al Nuaimi SA, Åhlman, H., Allen, Jj, Antonozzi, I., Archer, S., Au, S., Auray Blais, C., Baker, M., Bamforth, F., Beckmann, K., Pino, Gb, Berberich, Sl, Binard, R., Boemer, F., Bonham, J., Breen, Nn, Bryant, Sc, Caggana, M., Caldwell, Sg, Camilot, M., Campbell, C., Carducci, C., Cariappa, R., Carlisle, C., Caruso, U., Cassanello, M., Castilla, Am, Ramos, De, Chakraborty, P., Chandrasekar, R., Ramos, Ac, Cheillan, D., Chien, Yh, Childs, Ta, Chrastina, P., Sica, Yc, de Juan JA, Colandre, Me, Espinoza, Vc, Corso, G., Currier, R., Cyr, D., Czuczy, N., D Apolito, O., Davis, T., de Sain Van der Velden MG, Delgado Pecellin, C., Di Gangi IM, Di Stefano CM, Dotsikas, Y., Downing, M., Downs, Sm, Dy, B., Dymerski, M., Rueda, I., Elvers, B., Eaton, R., Eckerd, Bm, El Mougy, F., Eroh, S., Espada, M., Evans, C., Fawbush, S., Fijolek, Kf, Fisher, L., Franzson, L., Frazier, Dm, Garcia, Lr, Bermejo, Ms, Gavrilov, D., Gerace, R., Giordano, G., Irazabal, Yg, Greed, Lc, Grier, R., Grycki, E., Gu, X., Gulamali Majid, F., Hagar, Af, Han, L., Hannon, Wh, Haslip, C., Hassan, Fa, He, M., Hietala, A., Himstedt, L., Hoffman, Gl, Hoffman, W., Hoggatt, P., Hopkins, Pv, Hougaard, Dm, Hughes, K., Hunt, Pr, Hwu, Wl, Hynes, J., Ibarra González, I., Ingham, Ca, Ivanova, M., Jacox, Wb, John, C., Johnson, Jp, Jónsson, Jj, Karg, E., Kasper, D., Klopper, B., Katakouzinos, D., Khneisser, I., Knoll, D., Kobayashi, H., Koneski, R., Kozich, V., Kouapei, R., Kohlmueller, D., Kremensky, I., giancarlo la marca, Lavochkin, M., Lee, Sy, Lehotay, Dc, Lemes, A., Lepage, J., Lesko, B., Lewis, B., Lim, C., Linard, S., Lindner, M., Lloyd Puryear MA, Lorey, F., Loukas, Yl, Luedtke, J., Maffitt, N., Magee, Jf, Manning, A., Manos, S., Marie, S., Hadachi, Sm, Marquardt, G., Martin, Sj, Matern, D., Mayfield Gibson SK, Mayne, P., Mccallister, Td, Mccann, M., Mcclure, J., Mcgill, Jj, Mckeever, Cd, Mcneilly, B., Morrissey, Ma, Moutsatsou, P., Mulcahy, Ea, Nikoloudis, D., Norgaard Pedersen, B., Oglesbee, D., Oltarzewski, M., Ombrone, D., Ojodu, J., Papakonstantinou, V., Reoyo, Sp, Park, Hd, Pasquali, M., Pasquini, E., Patel, P., Pass, Ka, Peterson, C., Pettersen, Rd, Pitt, Jj, Poh, S., Pollak, A., Porter, C., Poston, Pa, Price, Rw, Queijo, C., Quesada, J., Randell, E., Ranieri, E., Raymond, K., Reddic, Je, Reuben, A., Ricciardi, C., Rinaldo, P., Rivera, Jd, Roberts, A., Rocha, H., Roche, G., Greenberg, Cr, Mellado, Jm, Juan Fita MJ, Ruiz, C., Ruoppolo, M., Rutledge, Sl, Ryu, E., Saban, C., Sahai, I., García Blanco MI, Santiago Borrero, P., Schenone, A., Schoos, R., Schweitzer, B., Scott, P., Seashore, Mr, Seeterlin, Ma, Sesser, De, Sevier, Dw, Shone, Sm, Sinclair, G., Skrinska, Va, Stanley, El, Strovel, Et, Jones, Al, Sunny, S., Takats, Z., Tanyalcin, T., Teofoli, F., Thompson, Jr, Tomashitis, K., Domingos, Mt, Torres, J., Torres, R., Tortorelli, S., Turi, S., Turner, K., Tzanakos, N., Valiente, Ag, Vallance, H., Vela Amieva, M., Vilarinho, L., Döbeln, U., Vincent, Mf, Vorster, Bc, Watson, Ms, Webster, D., Weiss, S., Wilcken, B., Wiley, V., Williams, Sk, Willis, Sa, Woontner, M., Wright, K., Yahyaoui, R., Yamaguchi, S., Yssel, M., Zakowicz, W. M., Mchugh, D, Cameron, Ca, Abdenur, Je, Abdulrahman, M, Adair, O, Al Nuaimi, Sa, Åhlman, H, Allen, Jj, Antonozzi, I, Archer, S, Au, S, Auray Blais, C, Baker, M, Bamforth, F, Beckmann, K, Pino, Gb, Berberich, Sl, Binard, R, Boemer, F, Bonham, J, Breen, Nn, Bryant, Sc, Caggana, M, Caldwell, Sg, Camilot, M, Campbell, C, Carducci, C, Cariappa, R, Carlisle, C, Caruso, U, Cassanello, M, Castilla, Am, Ramos, De, Chakraborty, P, Chandrasekar, R, Ramos, Ac, Cheillan, D, Chien, Yh, Childs, Ta, Chrastina, P, Sica, Yc, de Juan, Ja, Colandre, Me, Espinoza, Vc, Corso, G, Currier, R, Cyr, D, Czuczy, N, D'Apolito, O, Davis, T, de Sain Van der Velden, Mg, Delgado Pecellin, C, Di Gangi, Im, Di Stefano, Cm, Dotsikas, Y, Downing, M, Downs, Sm, Dy, B, Dymerski, M, Rueda, I, Elvers, B, Eaton, R, Eckerd, Bm, El Mougy, F, Eroh, S, Espada, M, Evans, C, Fawbush, S, Fijolek, Kf, Fisher, L, Franzson, L, Frazier, Dm, Garcia, Lr, Bermejo, M, Gavrilov, D, Gerace, R, Giordano, G, Irazabal, Yg, Greed, Lc, Grier, R, Grycki, E, Gu, X, Gulamali Majid, F, Hagar, Af, Han, L, Hannon, Wh, Haslip, C, Hassan, Fa, He, M, Hietala, A, Himstedt, L, Hoffman, Gl, Hoffman, W, Hoggatt, P, Hopkins, Pv, Hougaard, Dm, Hughes, K, Hunt, Pr, Hwu, Wl, Hynes, J, Ibarra González, I, Ingham, Ca, Ivanova, M, Jacox, Wb, John, C, Johnson, Jp, Jónsson, Jj, Karg, E, Kasper, D, Klopper, B, Katakouzinos, D, Khneisser, I, Knoll, D, Kobayashi, H, Koneski, R, Kozich, V, Kouapei, R, Kohlmueller, D, Kremensky, I, la Marca, G, Lavochkin, M, Lee, Sy, Lehotay, Dc, Lemes, A, Lepage, J, Lesko, B, Lewis, B, Lim, C, Linard, S, Lindner, M, Lloyd Puryear, Ma, Lorey, F, Loukas, Yl, Luedtke, J, Maffitt, N, Magee, Jf, Manning, A, Manos, S, Marie, S, Hadachi, Sm, Marquardt, G, Martin, Sj, Matern, D, Mayfield Gibson, Sk, Mayne, P, Mccallister, Td, Mccann, M, Mcclure, J, Mcgill, Jj, Mckeever, Cd, Mcneilly, B, Morrissey, Ma, Moutsatsou, P, Mulcahy, Ea, Nikoloudis, D, Norgaard Pedersen, B, Oglesbee, D, Oltarzewski, M, Ombrone, D, Ojodu, J, Papakonstantinou, V, Reoyo, Sp, Park, Hd, Pasquali, M, Pasquini, E, Patel, P, Pass, Ka, Peterson, C, Pettersen, Rd, Pitt, Jj, Poh, S, Pollak, A, Porter, C, Poston, Pa, Price, Rw, Queijo, C, Quesada, J, Randell, E, Ranieri, E, Raymond, K, Reddic, Je, Reuben, A, Ricciardi, C, Rinaldo, P, Rivera, Jd, Roberts, A, Rocha, H, Roche, G, Greenberg, Cr, Mellado, Jm, Juan Fita, Mj, Ruiz, C, Ruoppolo, Margherita, Rutledge, Sl, Ryu, E, Saban, C, Sahai, I, García Blanco, Mi, Santiago Borrero, P, Schenone, A, Schoos, R, Schweitzer, B, Scott, P, Seashore, Mr, Seeterlin, Ma, Sesser, De, Sevier, Dw, Shone, Sm, Sinclair, G, Skrinska, Va, Stanley, El, Strovel, Et, Jones, Al, Sunny, S, Takats, Z, Tanyalcin, T, Teofoli, F, Thompson, Jr, Tomashitis, K, Domingos, Mt, Torres, J, Torres, R, Tortorelli, S, Turi, S, Turner, K, Tzanakos, N, Valiente, Ag, Vallance, H, Vela Amieva, M, Vilarinho, L, von Döbeln, U, Vincent, Mf, Vorster, Bc, Watson, M, Webster, D, Weiss, S, Wilcken, B, Wiley, V, Williams, Sk, Willis, Sa, Woontner, M, Wright, K, Yahyaoui, R, Yamaguchi, S, Yssel, M, and Zakowicz, W. M.

Subjects
Analyte, Percentile, Pediatrics, medicine.medical_specialty, International Cooperation, tandem mass spectrometry, amino acids, newborn screening, inborn errors of metabolism, acylcarnitines, Tandem mass spectrometry, Sensitivity and Specificity, Neonatal Screening, Metabolic Diseases, Reference Values, Carnitine, Range (statistics), Humans, Medicine, Cutoff, Clinical significance, Genetics (clinical), mass spectrometry, Newborn screening, business.industry, Infant, Newborn, Biochemistry, False positive rate, business, Software, metabolic disorders, newborn screening
Abstract

Purpose: To achieve clinical validation of cutoff values for newborn screening by tandem mass 215 spectrometry through a worldwide collaboration. Methods: Cumulative percentiles of amino 216 acids and acylcarnitines in dried blood spots of approximately 30 million normal newborns and 217 10,615 true positive cases are compared to assign clinical significance, which is achieved when 218 the median of a disease range is either >99%ile or

Published
2011
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21. Biochimica Generale

Author

SALVATORE F, COLONNA G, AMMENDOLA R, BUSSOLINO F, CARSANA A, EMILIANI C, GIARDINA B, GIOVANE A, MINELLI A, PARENTE A, PORTA R, RIBONI L, RUOPPOLO M, TECCE M. F, TURCO M. C, VANONI M, ZANOTTI G., OLIVA, Adriana, CACCIAPUOTI, Giovanna, DELLA RAGIONE, Fulvio, PORCELLI, Marina, Salvatore, F, Colonna, G, Oliva, Adriana, Ammendola, R, Bussolino, F, Cacciapuoti, Giovanna, Carsana, A, DELLA RAGIONE, Fulvio, Emiliani, C, Giardina, B, Giovane, A, Minelli, A, Parente, A, Porcelli, Marina, Porta, R, Riboni, L, Ruoppolo, M, Tecce, M. F., Turco, M. C., Vanoni, M, and Zanotti, G.

Published
2013

23. The protein expression pattern of CD133+ colon cancer cells indicates activation of the Wnt pathway and potential alteration of splicing mechanisms

Author

Corbo, C, Orrù, S, Gemei, M, Di Noto, R, Mirabelli, P, Imperlini, E, Ruoppolo, M, Del Vecchio, L, Salvatore, F, Corbo C, Orrù S, Gemei M, Di Noto R, Mirabelli P, Imperlini E, Ruoppolo M, Del Vecchio L, Salvatore F, Corbo, C, Orrù, S, Gemei, M, Di Noto, R, Mirabelli, P, Imperlini, E, Ruoppolo, M, Del Vecchio, L, Salvatore, F, Corbo C, Orrù S, Gemei M, Di Noto R, Mirabelli P, Imperlini E, Ruoppolo M, Del Vecchio L, and Salvatore F

Published
2011

24. Comparative proteomics of CD133+and CD133-colon cancer cells reveals activation of the Wnt pathway and a potential therapeutic role of SRp20

Author

Corbo, C, Orru', Stefania, Gemei, M, Di Noto, R, Mirabelli, P, Imperlini, Esther, Ruoppolo, M, Del Vecchio, L, Salvatore, F., Corbo, C, Orrù, S, Gemei, M, Di Noto, R, Mirabelli, P, Imperlini, E, Ruoppolo, M, Del Vecchio, L, Salvatore, F, Stefania, O, Marica, G, Rosa Di, N, Peppino, M, Esther, I, Margherita, R, Luigi Del, V, and Francesco, S

Subjects
cancer stem cells, colon cancer, proteomics, biomarkers, cancer stem cells, colon cancer, proteomics
Published
2012

26. UNA BASSA ESPRESSIONE DELLA FOSFATASI SHP-1 CORRELA CON LA RESI-STENZA AL TRATTAMENTO CON INIBITORI DELLE TIROSIN KINASI IN PAZIENTIAFFETTI DA LEUCEMIA MIELOIDE CRONICA

Author

ESPOSITO, NICOLA, QUINTARELLI, CONCETTA, COLAVITA, IRENE, PELUSO, ANNA LUCIA, ERRICHIELLO, SANTA, DE ANGELIS, BIAGIO, MUSELLA, FILOMENA, IZZO, BARBARA, PISANO, IDA, Cacciapuoti, Valentina, LUCIANO, LUIGIA, Sica A. R., Muccioli Casadei G., Rinaldi P., Cosenza M., PICARDI, MARCO, Del Vecchio L., Buonomo T., Hughes T. P., Radich J. P., Russo D., Branford S., Saglio G., Melo J. V., Martinelli R., Ruoppolo M., Kalebic T., Martinelli G., Pane F., Esposito, N, Esposito, Nicola, Quintarelli, Concetta, Colavita, Irene, Sica, A. R., Peluso, ANNA LUCIA, Errichiello, Santa, DE ANGELIS, Biagio, Musella, Filomena, Izzo, Barbara, Muccioli Casadei, G., Rinaldi, P., Cosenza, M., Pisano, Ida, Cacciapuoti, Valentina, Luciano, Luigia, Picardi, Marco, Del Vecchio, L., Buonomo, T., Hughes, T. P., Radich, J. P., Russo, D., Branford, S., Saglio, G., Melo, J. V., Martinelli, R., Ruoppolo, M., Kalebic, T., Martinelli, G., and Pane, F.

Published
2011

28. Serum metabolomic profiles suggest influence of sex and oral contraceptive use

Author

Ruoppolo, M., ILARIA CAMPESI, Scolamiero, E., Pecce, R., Caterino, M., Cherchi, S., Mercuro, G., Tonolo, G., Franconi, F., Ruoppolo, Margherita, Campesi, I, Scolamiero, E, Pecce, R, Caterino, Marianna, Cherchi, S, Mercuro, G, Tonolo, G, and Franconi, F.

Abstract

Background The effects of sex and oral contraceptives (OCs) on blood metabolites have been scarcely studied. Considering the widespread use of OCs and the fact that protocol designs for clinical trials emphasise the use of contraception for women of childbearing potential, we examined if OCs and sex affect the serum levels of the physiologically relevant amino acids, carnitine and acylcarnitines, using metabolomics approaches. Methods Thirty-five healthy adult men and 67 women aged between 20 and 47 years were enrolled. They were drug free with the exception of women taking cyclic format OCs that contained ethinylestradiol and different progestins. OC-free women were analysed during the first ten days of their menstrual cycles, and amino acids, free carnitine and acylcarnitines were measured using HPLC or LC/MS/MS. Results The serum levels of alanine, serine, aspartic acid, arginine and taurine were not significantly different among the analysed groups. Men had significantly higher leucine, isoleucine, methionine, phenylalanine, asparagine, glutamine + glutamate, and histidine than women who did not use OCs, while tryptophan was significantly lower in men. OC use significantly decreased the levels of glycine, proline, glutamine + glutamate, lysine, hydroxyproline and ornitine when compared with non-user women. The level of free carnitine was higher in men than in women; in addition, OC use further reduced the levels of carnitine in women although the reduction is not significant. Total esterified carnitines were higher in untreated women when compared with that of men and OC users. Globally, the effect of OCs and sex was specific for the individual esterified carnitine. The observed metabolic changes were not attributable to renal or hepatic functions or to differences in body weight. Conclusion The assessed parameters were specifically influenced by sex, highlighting the need to have reference values for women and men. The major novelty of this study is the demonstration that OCs specifically change the profiles of serum amino acids and carnitine, which suggests that OC users and non-users should be represented in clinical trials.

Published
2014

30. Erythroid membrane proteomic

Author

Ruoppolo M., Orrù S., Savoia M., Iolascon A., Salvatore F., CATERINO, Marianna, Ruoppolo, M., Caterino, Marianna, Orrù, S., Savoia, M., Iolascon, A., and Salvatore, F.

Published
2004

32. The secretome signature of colon cancer cell lines

Author

Imperlini, Esther, Colavita, I, Caterino, M, Mirabelli, P, Pagnozzi, D, Del Vecchio, L, Di Noto, R, Ruoppolo, M, Orru', Stefania, Imperlini, Esther, Colavita, I, Caterino, Marianna, Mirabelli, P, Pagnozzi, D, DEL VECCHIO, Luigi, Di Noto, R, Ruoppolo, Margherita, and Orrù, S.

Subjects
Proteomics, Tandem Mass Spectrometry, Cell Line, Tumor, Blotting, Western, Colonic Neoplasms, Humans, Electrophoresis, Polyacrylamide Gel, Caco-2 Cells
Abstract

The definition of the secretome signature of a cancer cell line can be considered a potential tool to investigate tumor aggressiveness and a preclinical exploratory study required to optimize the search of cancer biomarkers. Dealing with a cell-specific secretome limits the contamination by the major components of the human serum and reduces the range of dynamic concentrations among the secreted proteins, thus favouring under-represented tissue-specific species. The aim of the present study is to characterize the secretome of two human colon carcinoma cell lines, CaCo-2 and HCT-GEO, in order to evaluate differences and similarities of two colorectal cancer model systems. In this study, we identified more than 170 protein species, 64 more expressed in the secretome of CaCo-2 cells and 54 more expressed in the secretome of HCT-GEO cells; 58 proteins were shared by the two systems. Among them, more than 50% were deemed to be secretory according to their Gene Ontology annotation and/or to their SignalP or SecretomeP scores. Such a characterization allowed corroborating the potential of a cell culture-based model in order to describe the cell-specific invasive properties and to provide a list of putative cancer biomarkers.

Published
2013

33. Enhanced interpretation of newborn screening results without analyte cutoff values

Author

Marquardt, G. Currier, R. McHugh, D.M.S. Gavrilov, D. Magera, M.J. Matern, D. Oglesbee, D. Raymond, K. Rinaldo, P. Smith, E.H. Tortorelli, S. Turgeon, C.T. Lorey, F. Wilcken, B. Wiley, V. Greed, L.C. Lewis, B. Boemer, F. Schoos, R. Marie, S. Vincent, M.-F. Sica, Y.C. Domingos, M.T. Al-Thihli, K. Sinclair, G. Al-Dirbashi, O.Y. Chakraborty, P. Dymerski, M. Porter, C. Manning, A. Seashore, M.R. Quesada, J. Reuben, A. Chrastina, P. Hornik, P. Atef Mandour, I. Atty Sharaf, S.A. Bodamer, O. Dy, B. Torres, J. Zori, R. Cheillan, D. Vianey-Saban, C. Ludvigson, D. Stembridge, A. Bonham, J. Downing, M. Dotsikas, Y. Loukas, Y.L. Papakonstantinou, V. Zacharioudakis, G.S.A. Baráth, K. Karg, E. Franzson, L. Jonsson, J.J. Breen, N.N. Lesko, B.G. Berberich, S.L. Turner, K. Ruoppolo, M. Scolamiero, E. Antonozzi, I. Carducci, C. Caruso, U. Cassanello, M. La Marca, G. Pasquini, E. Di Gangi, I.M. Giordano, G. Camilot, M. Teofoli, F. Manos, S.M. Peterson, C.K. Mayfield Gibson, S.K. Sevier, D.W. Lee, S.-Y. Park, H.-D. Khneisser, I. Browning, P. Gulamali-Majid, F. Watson, M.S. Eaton, R.B. Sahai, I. Ruiz, C. Torres, R. Seeterlin, M.A. Stanley, E.L. Hietala, A. McCann, M. Campbell, C. Hopkins, P.V. De Sain-Van Der Velden, M.G. Elvers, B. Morrissey, M.A. Sunny, S. Knoll, D. Webster, D. Frazier, D.M. McClure, J.D. Sesser, D.E. Willis, S.A. Rocha, H. Vilarinho, L. John, C. Lim, J. Caldwell, S.G. Tomashitis, K. Castĩeiras Ramos, D.E. Cocho De Juan, J.A. Rueda Fernández, I. Yahyaoui MacÍas, R. Egea-Mellado, J.M. González-Gallego, I. Delgado Pecellin, C. García-Valdecasas Bermejo, M.S. Chien, Y.-H. Hwu, W.-L. Childs, T. McKeever, C.D. Tanyalcin, T. Abdulrahman, M. Queijo, C. Lemes, A. Davis, T. Hoffman, W. Mei, B. Hoffman, G.L.

Abstract

Purpose: To improve quality of newborn screening by tandem mass spectrometry with a novel approach made possible by the collaboration of 154 laboratories in 49 countries. Methods: A database of 767,464 results from 12,721 cases affected with 60 conditions was used to build multivariate pattern recognition software that generates tools integrating multiple clinically significant results into a single score. This score is determined by the overlap between normal and disease ranges, penetration within the disease range, differences between conditions, and weighted correction factors. Results: Ninety tools target either a single condition or the differential diagnosis between multiple conditions. Scores are expressed as the percentile rank among all cases with the same condition and are compared to interpretation guidelines. Retrospective evaluation of past cases suggests that these tools could have avoided at least half of 279 false-positive outcomes caused by carrier status for fatty-acid oxidation disorders and could have prevented 88% of known false-negative events. Conclusion: Application of this computational approach to raw data is independent from single analyte cutoff values. In Minnesota, the tools have been a major contributing factor to the sustained achievement of a false-positive rate below 0.1% and a positive predictive value above 60%. © 2012 American College of Medical Genetics and Genomics.

Published
2012

34. Trattamento Palliativo Del Carcinoma Prostatico con Ipertermia: Nostra Esperienza

Author

Tombolini P, Ruoppolo M, S. Dell'Acqua, C. Zaatar, G. Mastromarino, and C. Bellorofonte

Subjects
business.industry, Medicine, General Medicine, business
Abstract

Between August 1992 and June 1993, 6 high surgical risk patients affected by prostatic cancer with serious irritative symptoms underwent prostatic transrectal hyperthermia (one application of 60 minutes twice a week for 5 times). Transrectal hyperthermic treatment showed good results in subjective symptomatology with rated changes in urinary flow, but without any change in the progression of the disease. Best results may be obtained in association with radiotherapy or chemotherapy.

Published
1994
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35. Derivazione ortotopica continente tipo emiKock: Nostra esperienza

Author

G. Mastromarino, C. Bellorofonte, P. Tombolini, A. Tagliaferri, C. Zaatar, Ruoppolo M, and S. Dell'Acqua

Subjects
General Medicine
Abstract

Between May 1991 and October 1993, 16 male patients with bladder neoplasms underwent surgical hemiKock's technique of continent urinary reservoir: 7 patients were staged T1, 4 patients were T2, 3 patients were T3 and 2 patients were T4. 5 patients underwent neo-adjuvant M-VAC chemotherapy before surgery, 2 patients underwent radiotherapy and 2 patients underwent adjuvant chemotherapy after surgery. Demolition of the bladder, prostate and seminal vesicles was made by both an ascending and descending manoeuvre, and was sectioned just below the veru montanum to spare the external urinary sphincter. In 7 patients we followed Walsh's technique to spare neurovascular bundles. 60 to 62 cm of small intestine was selected for reservoir construction, stopping 20-30 cm before the ileo-cecal valve. Particular care was adopted for construction of the antireflux nipple valve; uretero-ileal anastomosis was made following Wallace's technique. Mean term of surgery was 6 hours. Sovrapubic cystostomy was removed after 8 days, and urethral catheter after 21 days. After a mean follow up of 3-30 months our results are the following: 2 patients deceased for a pelvic relapse and general metastasis. In one patient we had a neoplastic relapse just on the ileo-urethral anastomosis, so permanent catheterism was necessary.

Published
1994
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37. Characterization of five new low-molecular-mass trypsin inhibitors from white mustard (Sinapis alba L.) seed RID A-4573-2009

Author

Ruoppolo M, Amoresano A, Pucci P, Pascarella S, Trovato M, Menegatti E, Ascenzi P., POLTICELLI, Fabio, Ruoppolo, M, Amoresano, A, Pucci, P, Pascarella, S, Polticelli, Fabio, Trovato, M, Menegatti, E, and Ascenzi, P.

Subjects
human activities
Abstract

Five new low-molecular-mass trypsin inhibitors belonging to the RTI/MTI-2 family were identified from white mustard (Sinapis alba L.; MTI-2) seed. Purified MTI-2 consisted of a peptide mixture, displaying Ile or Arg at position 43, Trp or kynurenine (Kyn) at position 44, and C-terminal ragged ends. The occurrence of Ile or Arg at position 43 suggested that MTI-2 inhibitors originated from different genes. The presence of 5-oxo-proline (pyroglutamic acid; 5-oxoPro1) and Kyn44 reflected post-translational processing of the serine proteinase inhibitor. MTI-2 showed approximate to 70% amino-acid identity with low-molecular-mass trypsin inhibitors isolated from oil rape (Brassica napus var. oleifera; RTI-III) seed and with serine proteinase inhibitors mapped in Arabidopsis thaliana chromosome II (ATTI). Furthermore, MTI-2 was homologous to brazzein, the sweet-tasting protein from Pentadiplandra brazzeana Baillon fruit (approximate to 30% amino-acid identity). Although snake-venom toxins showed a low amino-acid identity (< 20%) with MTI-2, RTI-III, and ATTI, some structurally relevant residues were conserved. The disulfide bridge pattern of MTI-2 (Cys5-Cys27, Cys18-Cys31, Cys42-Cys52, and Cys54-Cys57) corresponded to that of RTI-III and of snake-venom toxins, being different from that of brazzein. Therefore, protein similarity might be attributable to the three-dimensional arrangement rather than to the amino-acid sequence. Values of K-a for MTI-2 binding to bovine beta-trypsin (trypsin) and bovine alpha-chymotrypsin were 6.3 x 10(9) M-1 and 2.0 x 10(6) M-1, respectively, at pH 8.0 and 21.0 degrees C. Moreover, values of k(on) for MTI-2 binding to trypsin and of k(off) for the dissociation of the serine proteinase:inhibitor complex were 5.6 x 10(5) M-1.s(-1) and 8.9 x 10(-5) M-1.s(-1), respectively, at pH 8.0 and 21.0 degrees C. Despite the heterogeneity of the purified inhibitor peptide mixture, the inhibition properties of the different MTI-2 inhibitors were indistinguishable.

Published
2000

38. Characterisation of Five New Low-Molecular-Mass Trypsin Inhibitors from White Mustard (Sinapis alba L.) Seed

Author

RUOPPOLO M, AMORESANO A, PUCCI P, PASCARELLA S, POLTICELLI, Fabio, TROVATO M, MENEGATTI E, ASCENZI, Paolo, Ruoppolo, Margherita, Amoresano, A., Pucci, P., Pascarella, S., Polticelli, F., Trovato, M., Menegatti, E., Paolo, Ascenzi, Amoresano, Angela, Pucci, Pietro, Poltricelli, F., Ascenzi, P., Ruoppolo, M, Amoresano, A, Pucci, P, Pascarella, S, Polticelli, Fabio, Trovato, M, Menegatti, E, and Ascenzi, Paolo

Subjects
Spectrometry, Mass, Electrospray Ionization, inhibitory properties, Sinapis alba L, Molecular Sequence Data, disulfide bridge location, Thermolysin, trypsin inhibitors, amino-acid sequence determination, Sequence Analysis, Protein, Endopeptidases, Chymotrypsin, Trypsin, Amino Acid Sequence, Disulfides, Chromatography, High Pressure Liquid, Plant Proteins, Plants, Medicinal, Peptide Fragments, Molecular Weight, Kinetics, Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization, Seeds, Thermodynamics, Trypsin Inhibitors, Sequence Alignment, Mustard Plant
Abstract

Five new low-molecular-mass trypsin inhibitors belonging to the RTI/MTI-2 family were identified from white mustard (Sinapis alba L. ; MTI-2) seed. Purified MTI-2 consisted of a peptide mixture, displaying Ile or Arg at position 43, Trp or kynurenine (Kyn) at position 44, and C-terminal ragged ends. The occurrence of Ile or Arg at position 43 suggested that MTI-2 inhibitors originated from different genes. The presence of 5-oxo-proline (pyroglutamic acid; 5-oxoPro1) and Kyn44 reflected post-translational processing of the serine proteinase inhibitor. MTI-2 showed approximately 70% amino-acid identity with low-molecular-mass trypsin inhibitors isolated from oil rape (Brassica napus var. oleifera; RTI-III) seed and with serine proteinase inhibitors mapped in Arabidopsis thaliana chromosome II (ATTI). Furthermore, MTI-2 was homologous to brazzein, the sweet-tasting protein from Pentadiplandra brazzeana Baillon fruit ( approximately 30% amino-acid identity). Although snake-venom toxins showed a low amino-acid identity (20%) with MTI-2, RTI-III, and ATTI, some structurally relevant residues were conserved. The disulfide bridge pattern of MTI-2 (Cys5-Cys27, Cys18-Cys31, Cys42-Cys52, and Cys54-Cys57) corresponded to that of RTI-III and of snake-venom toxins, being different from that of brazzein. Therefore, protein similarity might be attributable to the three-dimensional arrangement rather than to the amino-acid sequence. Values of Ka for MTI-2 binding to bovine beta-trypsin (trypsin) and bovine alpha-chymotrypsin were 6.3 x 109 M-1 and 2.0 x 106 M-1, respectively, at pH 8.0 and 21.0 degrees C. Moreover, values of kon for MTI-2 binding to trypsin and of koff for the dissociation of the serine proteinase:inhibitor complex were 5.6 x 105 M-1.s-1 and 8.9 x 10-5 M-1.s-1, respectively, at pH 8.0 and 21.0 degrees C. Despite the heterogeneity of the purified inhibitor peptide mixture, the inhibition properties of the different MTI-2 inhibitors were indistinguishable.

Published
2000

40. Clinical validation of cutoff target ranges in newborn screening of metabolic disorders by tandem mass spectrometry: A worldwide collaborative project

Author

McHugh, D.M.S. Cameron, C.A. Abdenur, J.E. Abdulrahman, M. Adair, O. Al Nuaimi, S.A. Åhlman, H. Allen, J.J. Antonozzi, I. Archer, S. Au, S. Auray-Blais, C. Baker, M. Bamforth, F. Beckmann, K. Pino, G.B. Berberich, S.L. Binard, R. Boemer, F. Bonham, J. Breen, N.N. Bryant, S.C. Caggana, M. Caldwell, S.G. Camilot, M. Campbell, C. Carducci, C. Cariappa, R. Carlisle, C. Caruso, U. Cassanello, M. Castilla, A.M. Ramos, D.E.C. Chakraborty, P. Chandrasekar, R. Ramos, A.C. Cheillan, D. Chien, Y.-H. Childs, T.A. Chrastina, P. Sica, Y.C. Cocho De Juan, J.A. Colandre, M.E. Espinoza, V.C. Corso, G. Currier, R. Cyr, D. Czuczy, N. D'Apolito, O. Davis, T. De Sain-Van Der Velden, M.G. Pecellin, C.D. Di Gangi, I.M. Di Stefano, C.M. Dotsikas, Y. Downing, M. Downs, S.M. Dy, B. Dymerski, M. Rueda, I. Elvers, B. Eaton, R. Eckerd, B.M. El Mougy, F. Eroh, S. Espada, M. Evans, C. Fawbush, S. Fijolek, K.F. Fisher, L. Franzson, L. Frazier, D.M. Garcia, L.R.C. Bermejo, M.S.G.-V. Gavrilov, D. Gerace, R. Giordano, G. Irazabal, Y.G. Greed, L.C. Grier, R. Grycki, E. Gu, X. Gulamali-Majid, F. Hagar, A.F. Han, L. Hannon, W.H. Haslip, C. Hassan, F.A. He, M. Hietala, A. Himstedt, L. Hoffman, G.L. Hoffman, W. Hoggatt, P. Hopkins, P.V. Hougaard, D.M. Hughes, K. Hunt, P.R. Hwu, W.-L. Hynes, J. Ibarra-González, I. Ingham, C.A. Ivanova, M. Jacox, W.B. John, C. Johnson, J.P. Jónsson, J.J. Karg, E. Kasper, D. Klopper, B. Katakouzinos, D. Khneisser, I. Knoll, D. Kobayashi, H. Koneski, R. Kožich, V. Kouapei, R. Kohlmueller, D. Kremensky, I. La Marca, G. Lavochkin, M. Lee, S.-Y. Lehotay, D.C. Lemes, A. Lepage, J. Lesko, B. Lewis, B. Lim, C. Linard, S. Lindner, M. Lloyd-Puryear, M.A. Lorey, F. Loukas, Y.L. Luedtke, J. Maffitt, N. Magee, J.F. Manning, A. Manos, S. Marie, S. Hadachi, S.M. Marquardt, G. Martin, S.J. Matern, D. Gibson, S.K.M. Mayne, P. McCallister, T.D. McCann, M. McClure, J. McGill, J.J. McKeever, C.D. McNeilly, B. Morrissey, M.A. Moutsatsou, P. Mulcahy, E.A. Nikoloudis, D. Norgaard-Pedersen, B. Oglesbee, D. Oltarzewski, M. Ombrone, D. Ojodu, J. Papakonstantinou, V. Reoyo, S.P. Park, H.-D. Pasquali, M. Pasquini, E. Patel, P. Pass, K.A. Peterson, C. Pettersen, R.D. Pitt, J.J. Poh, S. Pollak, A. Porter, C. Poston, P.A. Price, R.W. Queijo, C. Quesada, J. Randell, E. Ranieri, E. Raymond, K. Reddic, J.E. Reuben, A. Ricciardi, C. Rinaldo, P. Rivera, J.D. Roberts, A. Rocha, H. Roche, G. Greenberg, C.R. Mellado, J.M.E. Juan-Fita, M.J. Ruiz, C. Ruoppolo, M. Rutledge, S.L. Ryu, E. Saban, C. Sahai, I. García-Blanco, M.I.S. Santiago-Borrero, P. Schenone, A. Schoos, R. Schweitzer, B. Scott, P. Seashore, M.R. Seeterlin, M.A. Sesser, D.E. Sevier, D.W. Shone, S.M. Sinclair, G. Skrinska, V.A. Stanley, E.L. Strovel, E.T. Jones, A.L.S. Sunny, S. Takats, Z. Tanyalcin, T. Teofoli, F. Thompson, J.R. Tomashitis, K. Domingos, M.T. Torres, J. Torres, R. Tortorelli, S. Turi, S. Turner, K. Tzanakos, N. Valiente, A.G. Vallance, H. Vela-Amieva, M. Vilarinho, L. Von Döbeln, U. Vincent, M.-F. Vorster, B.C. Watson, M.S. Webster, D. Weiss, S. Wilcken, B. Wiley, V. Williams, S.K. Willis, S.A. Woontner, M. Wright, K. Yahyaoui, R. Yamaguchi, S. Yssel, M. Zakowicz, W.M.

Abstract

PURPOSE:: To achieve clinical validation of cutoff values for newborn screening by tandem mass spectrometry through a worldwide collaborative effort. METHODS:: Cumulative percentiles of amino acids and acylcarnitines in dried blood spots of approximately 25-30 million normal newborns and 10,742 deidentified true positive cases are compared to assign clinical significance, which is achieved when the median of a disorder range is, and usually markedly outside, either the 99th or the 1st percentile of the normal population. The cutoff target ranges of analytes and ratios are then defined as the interval between selected percentiles of the two populations. When overlaps occur, adjustments are made to maximize sensitivity and specificity taking all available factors into consideration. RESULTS:: As of December 1, 2010, 130 sites in 45 countries have uploaded a total of 25,114 percentile data points, 565,232 analyte results of true positive cases with 64 conditions, and 5,341 cutoff values. The average rate of submission of true positive cases between December 1, 2008, and December 1, 2010, was 5.1 cases/day. This cumulative evidence generated 91 high and 23 low cutoff target ranges. The overall proportion of cutoff values within the respective target range was 42% (2,269/5,341). CONCLUSION:: An unprecedented level of cooperation and collaboration has allowed the objective definition of cutoff target ranges for 114 markers to be applied to newborn screening of rare metabolic disorders. © 2011 Lippincott Williams & Wilkins.

Published
2011

43. Reduced Expression Level of SHP1 Gives An Additive Survival Advantage to the Ph plus Cells of Chronic Myeloid Leukemia (CML) Patients and Provides a Novel Pretreatment Predictor of Major Molecular Response Achievement in CML Patients

Author

Esposito, N, Quintarelli, C, Colavita, I, Izzo, B, Peluso, AL, Ruoppolo, M, Del Vecchio, L, Russo, D, Branford, S, Iacobucci, I, Thornquist, M, Barnett, M, Melo, J, Saglio, G, Radich, J, Peter, L, Martinelli, G, Kalebic, T, Hughes, T, and Pane, F

Published
2010

47. Leech antihemostatic proteins share the T-knot scaffold, a disulfide-reinforced structural motif

Author

Ascenzi, P., Bolognesi, M., Daniele Catalucci, Pascarella, S., Ruoppolo, M., Rizzi, M., P., Ascenzi, M., Bolognesi, D., Catalucci, S., Pascarella, Ruoppolo, Margherita, M., Rizzi, Ascenzi, Paolo, Bolognesi, M, Catalucci, D, Pascarella, S, Ruoppolo, M, and Rizzi, M.

Subjects
Models, Molecular, decorsin, antistasin, egf-like proteins, hirudin, knottins, t-knot scaffold, Epidermal Growth Factor, Protein Conformation, Anticoagulants, Hirudins, Leeches, Animals, Humans, Trypsin Inhibitors
Abstract

The occurrence of similar topologies among unrelated proteins is an emerging theme in structural biology. Here we report that the T-knot scaffold, a disulfide-reinforced structural motif shared by knottins and EGF-like proteins, is also present in leech antihemostatic proteins. Our finding emphasizes the versatile nature of this small structural motif, representing a compact structural unit suitable for the diverse biological functions performed by knottins, EGF-like proteins and leech antihemostatic proteins.

Published
1998

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