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814 results on '"Sheaff, M"'

1. Pegargiminase Plus First-Line Chemotherapy in Patients With Nonepithelioid Pleural Mesothelioma

Author

Szlosarek, P, Creelan, B, Sarkodie, T, Nolan, L, Taylor, P, Olevsky, O, Grosso, F, Cortinovis, D, Chitnis, M, Roy, A, Gilligan, D, Kindler, H, Papadatos-Pastos, D, Ceresoli, G, Mansfield, A, Tsao, A, O’Byrne, K, Nowak, A, Steele, J, Sheaff, M, Shiu, C, Kuo, C, Johnston, A, Bomalaski, J, Zauderer, M, Fennell, D, Rybkin, I, Rolfo, C, Mackean, M, Steele, N, Franks, K, Shaw, P, Lind, M, Upadhyay, S, John, T, Karapetis, C, Srivastav, R, Mencoboni, M, Chella, A, Zilembo, N, de Marinis, F, Stella, M, Chong, I, Wang, C, Null, N, Szlosarek, Peter W., Creelan, Benjamin C., Sarkodie, Thomas, Nolan, Luke, Taylor, Paul, Olevsky, Olga, Grosso, Federica, Cortinovis, Diego, Chitnis, Meenali, Roy, Amy, Gilligan, David, Kindler, Hedy, Papadatos-Pastos, Dionysis, Ceresoli, Giovanni L., Mansfield, Aaron S., Tsao, Anne, O’Byrne, Kenneth J., Nowak, Anna K., Steele, Jeremy, Sheaff, Michael, Shiu, Chiung-Fang, Kuo, Chih-Ling, Johnston, Amanda, Bomalaski, John, Zauderer, Marjorie G., Fennell, Dean A., Rybkin, Igor I., Rolfo, Christian D., MacKean, Melanie, Steele, Nicola, Franks, Kevin, Shaw, Paul, Lind, Michael J., Upadhyay, Sunil, John, Thomas, Karapetis, Christos, Srivastav, Ratnesh, Mencoboni, Manlio, Chella, Antonio, Zilembo, Nicoletta, de Marinis, Filippo, Stella, Maria Giulia, Chong, Inn-Wen, Wang, Chin-Chou, null, null, Szlosarek, P, Creelan, B, Sarkodie, T, Nolan, L, Taylor, P, Olevsky, O, Grosso, F, Cortinovis, D, Chitnis, M, Roy, A, Gilligan, D, Kindler, H, Papadatos-Pastos, D, Ceresoli, G, Mansfield, A, Tsao, A, O’Byrne, K, Nowak, A, Steele, J, Sheaff, M, Shiu, C, Kuo, C, Johnston, A, Bomalaski, J, Zauderer, M, Fennell, D, Rybkin, I, Rolfo, C, Mackean, M, Steele, N, Franks, K, Shaw, P, Lind, M, Upadhyay, S, John, T, Karapetis, C, Srivastav, R, Mencoboni, M, Chella, A, Zilembo, N, de Marinis, F, Stella, M, Chong, I, Wang, C, Null, N, Szlosarek, Peter W., Creelan, Benjamin C., Sarkodie, Thomas, Nolan, Luke, Taylor, Paul, Olevsky, Olga, Grosso, Federica, Cortinovis, Diego, Chitnis, Meenali, Roy, Amy, Gilligan, David, Kindler, Hedy, Papadatos-Pastos, Dionysis, Ceresoli, Giovanni L., Mansfield, Aaron S., Tsao, Anne, O’Byrne, Kenneth J., Nowak, Anna K., Steele, Jeremy, Sheaff, Michael, Shiu, Chiung-Fang, Kuo, Chih-Ling, Johnston, Amanda, Bomalaski, John, Zauderer, Marjorie G., Fennell, Dean A., Rybkin, Igor I., Rolfo, Christian D., MacKean, Melanie, Steele, Nicola, Franks, Kevin, Shaw, Paul, Lind, Michael J., Upadhyay, Sunil, John, Thomas, Karapetis, Christos, Srivastav, Ratnesh, Mencoboni, Manlio, Chella, Antonio, Zilembo, Nicoletta, de Marinis, Filippo, Stella, Maria Giulia, Chong, Inn-Wen, Wang, Chin-Chou, and null, null

Abstract

IMPORTANCE Arginine deprivation using ADI-PEG20 (pegargiminase) combined with chemotherapy is untested in a randomized study among patients with cancer. ATOMIC-Meso (ADI-PEG20 Targeting of Malignancies Induces Cytotoxicity-Mesothelioma) is a pivotal trial comparing standard first-line chemotherapy plus pegargiminase or placebo in patients with nonepithelioid pleural mesothelioma. OBJECTIVE To determine the effect of pegargiminase-based chemotherapy on survival in nonepithelioid pleural mesothelioma, an arginine-auxotrophic tumor. DESIGN, SETTING, AND PARTICIPANTS Thiswas a phase 2-3, double-blind randomized clinical trial conducted at 43 centers in 5 countries that included patients with chemotherapy-naive nonepithelioid pleural mesothelioma from August 1, 2017, to August 15, 2021, with at least 12 months' follow-up. Final follow-up was on August 15, 2022. Data analysis was performed from March 2018 to June 2023. INTERVENTION Patients were randomly assigned (1:1) to receive weekly intramuscular pegargiminase (36.8mg/m2) or placebo. All patients received intravenous pemetrexed (500mg/m2) and platinum (75-mg/m2 cisplatin or carboplatin area under the curve 5) chemotherapy every 3 weeks up to 6 cycles. Pegargiminase or placebo was continued until progression, toxicity, or 24 months. MAIN OUTCOMES AND MEASURES The primary end pointwas overall survival, and secondary end points were progression-free survival and safety. Response rate by blinded independent central review was assessed in the phase 2 portion only. RESULTS Among 249 randomized patients (mean [SD] age, 69.5 [7.9] years; 43 female individuals [17.3%] and 206 male individuals [82.7%]), all were included in the analysis. The median overall survival was 9.3 months (95%CI, 7.9-11.8 months) with pegargiminase-chemotherapy as compared with 7.7 months (95%CI, 6.1-9.5 months) with placebo-chemotherapy (hazard ratio [HR] for death, 0.71; 95%CI, 0.55-0.93; P = .02). The median progression-free survival was 6.2 months (

Published
2024

3. Asymmetries in the Production of Lambda0 in 250 GeV/c pi+-, K+- and p -- Nucleon Interactions

Author

Alves, G. A., Amato, S., Anjos, J. C., Appel, J. A., Astorga, J., Bernard, T., Bracker, S. B., Cremaldi, L. M., Dagenhart, W. D., Darling, C. L., Errede, D., Fenker, H. C., Gay, C., Green, D. R., Jedicke, R., Karchin, P. E., Kwan, S., Lueking, L. H., Neto, J. R. T. de Mello, Metheny, J., Milburn, R. H., de Miranda, J. M., da Motta, H., Napier, A., Nicola, M. S., Passmore, D., Rafatian, A., Reis, A. C. dos, Ross, W. R., Santoro, A. F. S., Sheaff, M., Souza, M. H. G., Stoughton, C., Streetman, M. E., Summers, D. J., Takach, S. F., Wallace, A., and Wu, Z.

Subjects
High Energy Physics - Experiment
Abstract

Using data from Fermilab fixed-target experiment E769, we have measured particle-antiparticle production asymmetries for Lambda0 hyperons in 250 GeV/c pi+-, K+- and p -- nucleon interactions. The asymmetries are measured as functions of Feynman-x (x_F) and p_t^2 over the ranges -0.12<=x_F<=0.12 and 0<=p_t^2<=3 (GeV/c)^2 (for positive beam) and -0.12<=x_F<=0.4 and 0<=p_t^2<=10 (GeV/c)^2 (for negative beam). We find substantial asymmetries, even at x_F around zero. We also observe leading-particle-type asymmetries. These latter effects are qualitatively as expected from valence-quark content of the target and variety of projectiles studied., Comment: 14 pages, 4 figures

Published
2003
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4. BAK and NOXA Are Critical Determinants of Mitochondrial Apoptosis Induced by Bortezomib in Mesothelioma

Author

Broaddus, V Courtney, Busacca, S, Chacko, AD, Klabatsa, A, Arthur, K, Sheaff, M, Gunasekharan, VK, Gorski, JJ, El-Tanani, M, Broaddus, VC, and Gaudino, G

Abstract

Based on promising preclinical efficacy associated with the 20S proteasome inhibitor bortezomib in malignant pleural mesothelioma (MPM), two phase II clinical trials have been initiated (EORTC 08052 and ICORG 05-10). However, the potential mechanisms under

Published
2013

6. Asymmetries between the production of D+ and D- mesons from 500 GeV/c pi- nucleon interactions as a function of xF and pt**2

Author

Aitala, E. M., Amato, S., Anjos, J. C., Appel, J. A., Aryal, M., Ashery, D., Astorga, J., Banerjee, S., Bediaga, I., Blaylock, G., Bracker, S. B., Burchat, P. R., Burnstein, R. A., Carter, T., Carvalho, H. S., Costa, I., Cremaldi, L. M., Darling, C., Denisenko, K., Fernandez, A., Gagnon, P., Gerzon, S., Gobel, C., Gounder, K., Granite, D., Halling, A. M., Herrera, G., Hurvits, G., James, C., Kasper, P. A., Kondakis, N., Kwan, S., Langs, D. C., Leslie, J., Lichtenstadt, J., Lundberg, B., Manacero, A., MayTal-Beck, S., Meadows, B., Neto, J. R. T. de Mello, Milburn, R. H., de Miranda, J. M., Napier, A., Nguyen, A., d'Oliveira, A. B., O'Shaughnessy, K., Peng, K. C., Perera, L. P., Purohit, M. V., Quinn, B., Radeztsky, S., Rafatian, A., Reay, N. W., Reidy, J. J., Reis, A. C., Rubin, H. A., Santha, A. K. S., Santoro, A. F. S., Schwartz, A. J., Sheaff, M., Sidwell, R. A., Slaughter, A. J., Smith, J. G., Sokoloff, M. D., Stanton, N. R., Sugano, K., Summers, D. J., Takach, S., Thorne, K., Tripathi, A. K., Watanabe, S., Weiss-Babai, R., Wiener, J., Witchey, N., Wolin, E., Yi, D., Zaliznyak, R., and Zhang, C.

Subjects
High Energy Physics - Experiment
Abstract

We present asymmetries between the production of D+ and D- mesons in Fermilab experiment E791 as a function of xF and pt**2. The data used here consist of 74,000 fully-reconstructed charmed mesons produced by a 500 GeV/c pi- beam on C and Pt foils. The measurements are compared to results of models which predict differences between the production of heavy-quark mesons that have a light quark in common with the beam (leading particles) and those that do not (non-leading particles). While the default models do not agree with our data, we can reach agreement with one of them, PYTHIA, by making a limited number of changes to parameters used.

Published
1996
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9. Cancer Risk Stratification of Anal Intraepithelial Neoplasia in Human Immunodeficiency Virus-Positive Men by Validated Methylation Markers Associated With Progression to Cancer

Author

Zee, R.P. van der, Richel, O., Noesel, C.J. van, Ciocănea-Teodorescu, I., Splunter, A.P. van, Braak, T.J. Ter, Nathan, M., Cuming, T., Sheaff, M., Kreuter, A., Meijer, C., Quint, W.G., Vries, H.J.C. de, Prins, J.M., Steenbergen, R.D., Zee, R.P. van der, Richel, O., Noesel, C.J. van, Ciocănea-Teodorescu, I., Splunter, A.P. van, Braak, T.J. Ter, Nathan, M., Cuming, T., Sheaff, M., Kreuter, A., Meijer, C., Quint, W.G., Vries, H.J.C. de, Prins, J.M., and Steenbergen, R.D.

Abstract

Contains fulltext : 235261.pdf (Publisher’s version ) (Open Access), BACKGROUND: High-grade anal intraepithelial neoplasia (HGAIN; AIN2-3) is highly prevalent in HIV+ men, but only a minority of these lesions progress towards cancer. Currently, cancer progression risk cannot be established; therefore, no consensus exists on whether HGAIN should be treated. This study aimed to validate previously identified host cell DNA methylation markers for detection and cancer risk stratification of HGAIN. METHODS: A large independent cross-sectional series of 345 anal cancer, AIN3, AIN2, AIN1, and normal control biopsies of HIV+ men was tested for DNA methylation of 6 genes using quantitative methylation-specific PCR. We determined accuracy for detection of AIN3 and cancer (AIN3+) by univariable and multivariable logistic regression analysis, followed by leave-one-out cross-validation. Methylation levels were assessed in a series of 10 anal cancer cases with preceding HGAIN at similar anatomic locations, and compared with the cross-sectional series. RESULTS: Methylation levels of all genes increased with increasing severity of disease (P < .05). HGAIN revealed a heterogeneous methylation pattern, with a subset resembling cancer. ZNF582 showed highest accuracy (AUC = 0.88) for AIN3+ detection, slightly improved by addition of ASCL1 and SST (AUC = 0.89), forming a marker panel. In the longitudinal series, HGAIN preceding cancer displayed high methylation levels similar to cancers. CONCLUSIONS: We validated the accuracy of 5 methylation markers for the detection of anal (pre-) cancer. High methylation levels in HGAIN were associated with progression to cancer. These markers provide a promising tool to identify HGAIN in need of treatment, preventing overtreatment of HGAIN with a low cancer progression risk.

Published
2021

11. Correlations between D and $${\overline D}$$ mesons produced in 500 GeV/cπ−-nucleon interactions

Author

Aitala, E. M., Amato, S., Anjos, J. C., Appel, J. A., Ashery, D., Banerjee, S., Bediaga, I., Blaylock, G., Bracker, S. B., Burchat, P. R., Burnstein, R. A., Carter, T., Carvalho, H. S., Copty, N. K., Cremaldi, L. M., Darling, C., Denisenko, K., Fernandez, A., Fox, G. F., Gagnon, P., Gobel, C., Gounder, K., Halling, A. M., Herrera, G., Hurvits, G., James, C., Kasper, P. A., Kwan, S., Langs, D. C., Leslie, J., Lundberg, B., MayTal-Beck, S., Meadows, B., de Mello Neto, J.R.T., Mihalcea, D., Milburn, R. H., de Miranda, J.M., Napier, A., Nguyen, A., d’Oliveira, A.B., O’Shaughnessy, K., Peng, K.C., Perera, L.P., Purohit, M.V., Quinn, B., Radeztsky, S., Rafatian, A., Reay, N.W., Reidy, J.J., dos Reis, A.C., Rubin, H.A., Sanders, D.A., Santha, A.K.S., Santoro, A.F.S., Schwartz, A.J., Sheaff, M., Sidwell, R.A., Slaughter, A.J., Sokoloff, M.D., Solano, J., Stanton, N.R., Stefanski, R.J., Stenson, K., Summers, D.J., Takach, S., Thorne, K., Tripathi, A.K., Watanabe, S., Weiss-Babai, R., Wiener, J., Witchey, N., Wolin, E., Yang, S.M., Yi, D., Yoshida, S., Zaliznyak, R., and Zhang, C.

Published
2000
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16. Application of genetic programming to high energy physics event selection

Author

Link, J.M., Yager, P.M., Anjos, J.C., Bediaga, I., Castromonte, C., Göbel, C., Machado, A.A., Magnin, J., Massafferri, A., de Miranda, J.M., Pepe, I.M., Polycarpo, E., dos Reis, A.C., Carrillo, S., Casimiro, E., Cuautle, E., Sánchez-Hernández, A., Uribe, C., Vázquez, F., Agostino, L., Cinquini, L., Cumalat, J.P., O’Reilly, B., Segoni, I., Stenson, K., Butler, J.N., Cheung, H.W.K., Chiodini, G., Gaines, I., Garbincius, P.H., Garren, L.A., Gottschalk, E., Kasper, P.H., Kreymer, A.E., Kutschke, R., Wang, M., Benussi, L., Bertani, M., Bianco, S., Fabbri, F.L., Pacetti, S., Zallo, A., Reyes, M., Cawlfield, C., Kim, D.Y., Rahimi, A., Wiss, J., Gardner, R., Kryemadhi, A., Chung, Y.S., Kang, J.S., Ko, B.R., Kwak, J.W., Lee, K.B., Cho, K., Park, H., Alimonti, G., Barberis, S., Boschini, M., Cerutti, A., D’Angelo, P., DiCorato, M., Dini, P., Edera, L., Erba, S., Inzani, P., Leveraro, F., Malvezzi, S., Menasce, D., Mezzadri, M., Moroni, L., Pedrini, D., Pontoglio, C., Prelz, F., Rovere, M., Sala, S., Davenport, T.F., III, Arena, V., Boca, G., Bonomi, G., Gianini, G., Liguori, G., Lopes Pegna, D., Merlo, M.M., Pantea, D., Ratti, S.P., Riccardi, C., Vitulo, P., Hernandez, H., Lopez, A.M., Mendez, H., Paris, A., Quinones, J., Ramirez, J.E., Zhang, Y., Wilson, J.R., Handler, T., Mitchell, R., Engh, D., Hosack, M., Johns, W.E., Luiggi, E., Moore, J.E., Nehring, M., Sheldon, P.D., Vaandering, E.W., Webster, M., and Sheaff, M.

Published
2005
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18. Banff ʼ05 Meeting Report: Differential Diagnosis of Chronic Allograft Injury and Elimination of Chronic Allograft Nephropathy (‘CAN’)

Author

Solez, K., Colvin, R. B., Racusen, L. C., Sis, B., Halloran, P. F., Birk, P. E., Campbell, P. M., Cascalho, M., Collins, A. B., Demetris, A. J., Drachenberg, C. B., Gibson, I. W., Grimm, P. C., Haas, M., Lerut, E., Liapis, H., Mannon, R. B., Marcus, P. B., Mengel, M., Mihatsch, M. J., Nankivell, B. J., Nickeleit, V., Papadimitriou, J. C., Platt, J. L., Randhawa, P., Roberts, I., Salinas-Madriga, L., Salomon, D. R., Seron, D., Sheaff, M., and Weening, J. J.

Published
2007

26. The target silicon detector for the FOCUS spectrometer

Author

Link, J.M, Reyes, M, Yager, P.M, Anjos, J.C, Bediaga, I, Göbel, C, Magnin, J, Massafferri, A, de Miranda, J.M, Pepe, I.M, dos Reis, A.C, Carrillo, S, Casimiro, E, Cuautle, E, Sánchez-Hernández, A, Uribe, C, Vázquez, F, Agostino, L, Cinquini, L, Cumalat, J.P, O'Reilly, B, Ramirez, J.E, Segoni, I, Butler, J.N, Cheung, H.W.K, Chiodini, G, Gaines, I, Garbincius, P.H, Garren, L.A, Gottschalk, E, Kasper, P.H, Kreymer, A.E, Kutschke, R, Benussi, L, Bianco, S, Fabbri, F.L, Zallo, A, Cawlfield, C, Kim, D.Y, Rahimi, A, Wiss, J, Gardner, R, Kryemadhi, A, Chung, Y.S, Kang, J.S, Ko, B.R, Kwak, J.W, Lee, K.B, Cho, K, Park, H, Alimonti, G, Barberis, S, Boschini, M, D'Angelo, P, DiCorato, M, Dini, P, Edera, L, Erba, S, Giammarchi, M, Inzani, P, Leveraro, F, Malvezzi, S, Menasce, D, Mezzadri, M, Milazzo, L, Moroni, L, Pedrini, D, Pontoglio, C, Prelz, F, Rovere, M, Sala, S, Davenport III, T.F, Arena, V, Boca, G, Bonomi, G, Gianini, G, Liguori, G, Merlo, M.M, Pantea, D, Ratti, S.P, Riccardi, C, Vitulo, P, Hernandez, H, Lopez, A.M, Mendez, H, Mendez, L, Montiel, E, Olaya, D, Paris, A, Quinones, J, Rivera, C, Xiong, W, Zhang, Y, Purohit, M, Copty, N, Wilson, J.R, Handler, T, Mitchell, R, Engh, D, Helms, R.W, Hosack, M, Johns, W.E, Nehring, M, Sheldon, P.D, Stenson, K, Webster, M, and Sheaff, M

Published
2004
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40. Reconstruction of Vees, Kinks, Ξ −'s, and [formula omitted]'s in the FOCUS spectrometer

Author

Link, J.M., Reyes, M., Yager, P.M., Anjos, J.C., Bediaga, I., Göbel, C., Magnin, J., Massafferri, A., de Miranda, J.M., Pepe, I.M., dos Reis, A.C., Carrillo, S., Casimiro, E., Cuautle, E., Sánchez-Hernández, A., Uribe, C., Vázquez, F., Cinquini, L., Cumalat, J.P., O'Reilly, B., Ramirez, J.E., Vaandering, E.W., Butler, J.N., Cheung, H.W.K., Gaines, I., Garbincius, P.H., Garren, L.A., Gottschalk, E., Kasper, P.H., Kreymer, A.E., Kutschke, R., Bianco, S., Fabbri, F.L., Sarwar, S., Zallo, A., Cawlfield, C., Kim, D.Y., Rahimi, A., Wiss, J., Gardner, R., Kryemadhi, A., Chung, Y.S., Kang, J.S., Ko, B.R., Kwak, J.W., Lee, K.B., Park, H., Alimonti, G., Boschini, M., D'Angelo, P., DiCorato, M., Dini, P., Giammarchi, M., Inzani, P., Leveraro, F., Malvezzi, S., Menasce, D., Mezzadri, M., Milazzo, L., Moroni, L., Pedrini, D., Pontoglio, C., Prelz, F., Rovere, M., Sala, S., Davenport III, T.F., Agostino, L., Arena, V., Boca, G., Bonomi, G., Gianini, G., Liguori, G., Merlo, M.M., Pantea, D., Ratti, S.P., Riccardi, C., Segoni, I., Vitulo, P., Hernandez, H., Lopez, A.M., Mendez, H., Mendez, L., Montiel, E., Olaya, D., Paris, A., Quinones, J., Rivera, C., Xiong, W., Zhang, Y., Wilson, J.R., Cho, K., Handler, T., Mitchell, R., Engh, D., Hosack, M., Johns, W.E., Nehring, M., Sheldon, P.D., Stenson, K., Webster, M., and Sheaff, M.

Published
2002
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41. Cherenkov particle identification in FOCUS

Author

Link, J.M, Reyes, M, Yager, P.M, Anjos, J.C, Bediaga, I, Göbel, C, Magnin, J, Massafferri, A, de Miranda, J.M, Pepe, I.M, dos Reis, A.C, Carrillo, S, Casimiro, E, Cuautle, E, Sánchez-Hernández, A, Uribe, C, Vazquez, F, Cinquini, L, Cumalat, J.P, O'Reilly, B, Ramirez, J.E, Vaandering, E.W, Butler, J.N, Cheung, H.W.K, Gaines, I, Garbincius, P.H, Garren, L.A, Gottschalk, E, Kasper, P.H, Kreymer, A.E, Kutschke, R, Bianco, S, Fabbri, F.L, Sarwar, S, Zallo, A, Cawlfield, C, Kim, D.Y, Park, K.S, Rahimi, A, Wiss, J, Gardner, R, Kryemadhi, A, Chung, Y.S, Kang, J.S, Ko, B.R, Kwak, J.W, Lee, K.B, Park, H, Alimonti, G, Boschini, M, D'Angelo, P, DiCorato, M, Dini, P, Giammarchi, M, Inzani, P, Leveraro, F, Malvezzi, S, Menasce, D, Mezzadri, M, Milazzo, L, Moroni, L, Pedrini, D, Pontoglio, C, Prelz, F, Rovere, M, Sala, S, Davenport III, T.F, Agostino, L, Arena, V, Boca, G, Bonomi, G, Gianini, G, Liguori, G, Merlo, M.M, Pantea, D, Ratti, S.P, Riccardi, C, Segoni, I, Vitulo, P, Hernandez, H, Lopez, A.M, Mendez, H, Mendez, L, Montiel, E, Olaya, D, Paris, A, Quinones, J, Rivera, C, Xiong, W, Zhang, Y, Wilson, J.R, Cho, K, Handler, T, Mitchell, R, Engh, D, Johns, W.E, Hosack, M, Nehring, M.S, Sheldon, P.D, Stenson, K, Webster, M.S, and Sheaff, M

Published
2002
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45. British Lung Foundation/United Kingdom Primary Immunodeficiency Network Consensus Statement on the Definition, Diagnosis, and Management of Granulomatous-Lymphocytic Interstitial Lung Disease in Common Variable Immunodeficiency Disorders\ud

Author

Hurst, J.R., Verma, N., Lowe, D., Baxendale, H.E., Jolles, S., Kelleher, P., Longhurst, H.J., Patel, S.Y., Renzoni, E.A., Sander, C.R., Avery, G.R., Babar, J.L., Buckland, M.S., Burns, S., Egner, W., Gompels, M.M., Gordins, P., Haddock, J.A., Hart, S.P., Hayman, G.R., Herriot, R., Hoyles, R.K., Huissoon, A.P., Jacob, J., Nicholson, A.G., Rassl, D.M., Sargur, R.B., Savic, S., Seneviratne, S.L., Sheaff, M., Vaitla, P.M., Walters, G.I., Whitehouse, J.L., Wright, P.A., and Condliffe, A.M.

Published
2017

46. Phase 1 Dose-Escalation Study of Pegylated Arginine Deiminase, Cisplatin, and Pemetrexed in Patients With Argininosuccinate Synthetase 1-Deficient Thoracic Cancers

Author

Beddowes, E, Spicer, J, Chan, PY, Khadeir, R, Corbacho, JG, Repana, D, Steele, JP, Schmid, P, Szyszko, T, Cook, G, Diaz, M, Feng, X, Johnston, A, Thomson, J, Sheaff, M, Wu, B-W, Bomalaski, J, Pacey, S, Szlosarek, PW, Beddowes, Emma [0000-0001-7649-2863], Pacey, Simon [0000-0002-3303-7577], and Apollo - University of Cambridge Repository

Subjects
Male, Mesothelioma, Lung Neoplasms, Dose-Response Relationship, Drug, Hydrolases, Pleural Neoplasms, Mesothelioma, Malignant, Pemetrexed, Argininosuccinate Synthase, Middle Aged, Polyethylene Glycols, Carcinoma, Non-Small-Cell Lung, Antineoplastic Combined Chemotherapy Protocols, Humans, Female, Cisplatin, Aged
Abstract

Purpose: Pegylated arginine deiminase (ADI-PEG 20) depletes essential amino acid levels in argininosuccinate synthetase 1 (ASS1) -negative tumors by converting arginine to citrulline and ammonia. The main aim of this study was to determine the recommended dose, safety, and tolerability of ADI-PEG 20, cisplatin, and pemetrexed in patients with ASS1-deficient malignant pleural mesothelioma (MPM) or non-small-cell lung cancer (NSCLC). Patients and Methods: Using a 3 + 3 + 3 dose-escalation study, nine chemotherapy-naïve patients (five MPM, four NSCLC) received weekly ADI-PEG 20 doses of 18 mg/m(2), 27 mg/m(2), or 36 mg/m(2), together with pemetrexed 500 mg/m(2) and cisplatin 75 mg/m(2) which were given every three weeks (maximum of six cycles). Patients achieving stable disease or better could continue ADI-PEG 20 monotherapy until disease progression or withdrawal. Adverse events were assessed by Common Terminology Criteria for Adverse Events version 4.03, and pharmacodynamics and immunogenicity were also evaluated. Tumor response was assessed by Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1 for NSCLC and by modified RECIST criteria for MPM. Results: No dose-limiting toxicities were reported; nine of 38 reported adverse events (all grade 1 or 2) were related to ADI-PEG 20. Circulating arginine concentrations declined rapidly, and citrulline levels increased; both changes persisted at 18 weeks. Partial responses were observed in seven of nine patients (78%), including three with either sarcomatoid or biphasic MPM. Conclusion: Target engagement with depletion of arginine was maintained throughout treatment with no dose-limiting toxicities. In this biomarker-selected group of patients with ASS1-deficient cancers, clinical activity was observed in patients with poor-prognosis tumors. Therefore, we recommend a dose for future studies of weekly ADI-PEG 20 36 mg/m(2) plus three-weekly cisplatin 75 mg/m(2) and pemetrexed 500 mg/m(2).dose-limiting toxicities. In this biomarker-selected group of patients withASS1-deficient cancers, clinical activity was observed in patients withpoor-prognosis tumors. Therefore, we recommend a dose for future studies of weekly ADI-PEG 20 36 mg/m(2) plus three-weekly cisplatin 75mg/m(2) and pemetrexed 500 mg/m(2).

Published
2017

47. Phylogenetic ctDNA analysis depicts early stage lung cancer evolution

Author

Abbosh, C, Birkbak, NJ, Wilson, GA, Jamal-Hanjani, M, Constantin, T, Salari, R, Quesne, JL, Moore, DA, Veeriah, S, Rosenthal, R, Marafioti, T, Kirkizlar, E, Watkins, TBK, McGranahan, N, Ward, S, Martinson, L, Riley, J, Fraioli, F, Bakir, MA, GrÖnroos, E, Zambrana, F, Endozo, R, Bi, WL, Fennessy, FM, Sponer, N, Johnson, D, Laycock, J, Shafi, S, Czyzewska-Khan, J, Rowan, A, Chambers, T, Matthews, N, Turajlic, S, Hiley, C, Lee, SM, Forster, MD, Ahmad, T, Falzon, M, Borg, E, Lawrence, D, Hayward, M, Kolvekar, S, Panagiotopoulos, N, Janes, SM, Thakrar, R, Ahmed, A, Blackhall, F, Summers, Y, Hafez, D, Naik, A, Ganguly, A, Kareht, S, Shah, R, Joseph, L, Quinn, AM, Crosbie, P, Naidu, B, Middleton, G, Langman, G, Trotter, S, Nicolson, M, Remmen, H, Kerr, K, Chetty, M, Gomersall, L, Fennell, DA, Nakas, A, Rathinam, S, Anand, G, Khan, S, Russell, P, Ezhil, V, Ismail, B, Irvin-sellers, M, Prakash, V, Lester, JF, Kornaszewska, M, Attanoos, R, Adams, H, Davies, H, Oukrif, D, Akarca, AU, Hartley, JA, Lowe, HL, Lock, S, Iles, N, Bell, H, Ngai, Y, Elgar, G, Szallasi, Z, Schwarz, RF, Herrero, J, Stewart, A, Quezada, SA, Van Loo, P, Dive, C, Lin, CJ, Rabinowitz, M, Aerts, HJWL, Hackshaw, A, Shaw, JA, Zimmermann, BG, Swanton, C, Bosshard-Carter, L, Goh, G, Gorman, P, Murugaesu, N, Hynds, RE, Wilson, G, Horswell, S, Al Bakir, M, Mitter, R, Escudero, M, Xu, H, Goldman, J, Stone, RK, Denner, T, Biggs, J, Costa, M, Begum, S, Phillimore, B, Nye, E, Graca, S, Joshi, K, Furness, A, Aissa, AB, Wong, YNS, Georgiou, A, Quezada, S, Simeon, C, Hector, G, Smith, A, Aranda, M, Novelli, M, Forster, M, Papadatos-Pastos, D, Carnell, D, Mendes, R, George, J, Navani, N, Taylor, M, Choudhary, J, Califano, R, Taylor, P, Krysiak, P, Rammohan, K, Fontaine, E, Booton, R, Evison, M, Moss, S, Idries, F, Bishop, P, Chaturved, A, Marie Quinn, A, Doran, H, leek, A, Harrison, P, Moore, K, Waddington, R, Novasio, J, Rogan, J, Smith, E, Tugwood, J, Brady, G, Rothwell, DG, Chemi, F, Pierce, J, Gulati, S, Bellamy, M, Bancroft, H, Kerr, A, Kadiri, S, Webb, J, Djearaman, M, Fennell, D, Le Quesne, J, Moore, D, Thomas, A, Walter, H, Monteiro, W, Marshall, H, Nelson, L, Bennett, J, Primrose, L, Amadi, A, Palmer, S, Miller, J, Buchan, K, Lester, J, Edwards, A, Morgan, F, Verjee, A, MacKenzie, M, Wilcox, M, Smith, S, Gower, N, Ottensmeier, C, Chee, S, Johnson, B, Alzetani, A, Shaw, E, Lim, E, De Sousa, P, Tavares Barbosa, M, Bowman, A, Jordan, S, Rice, A, Raubenheimer, H, Proli, C, Elena Cufari, M, Ronquillo, JC, Kwayie, A, Bhayani, H, Hamilton, M, Bakar, Y, Mensah, N, Ambrose, L, Devaraj, A, Buderi, S, Finch, J, Azcarate, L, Chavan, H, Green, S, Mashinga, H, Nicholson, AG, Lau, K, Sheaff, M, Schmid, P, Conibear, J, Light, T, Horey, T, Danson, S, Bury, J, Edwards, J, Hill, J, Matthews, S, Kitsanta, Y, Suvarna, K, Fisher, P, Keerio, AD, Shackcloth, M, Gosney, J, Postmus, P, Feeney, S, Asante-Siaw, J, Constatin, T, Zimmermann, B, Dentro, S, Dessimoz, C, Shiu, K-K, Bridgewater, J, Hochauser, D, Beck, S, Parker, P, Walczak, H, Enver, T, Proctor, I, Sinclair, R, Lok, C-W, Mitchison, M, Trevisan, G, Lynch, M, Brandner, S, Gishen, F, Tookman, A, Stone, P, Sterling, C, Larkin, J, Attard, G, Eeles, R, Foster, C, Bova, S, Sottoriva, A, Chowdhury, S, Ashish, C, Spicer, J, Stares, M, Lynch, J, Caldas, C, Brenton, J, Fitzgerald, R, Jimenez-Linan, M, Provenzano, E, Cluroe, A, Stewart, G, Watts, C, Gilbertson, R, McDermott, U, Tavare, S, Maughan, T, Tomlinson, I, Campbell, P, McNeish, I, Biankin, A, Chambers, A, Fraser, S, Oien, K, Krebs, M, Marais, R, Carter, L, Nonaka, D, Dhomen, N, Shaw, J, Baijal, S, Tanchel, B, Collard, M, Cockcroft, P, Taylor, J, Colloby, P, Olisemeke, B, Wilson, R, Harrison, D, Loda, M, Flanagan, A, McKenzie, M, Lederman, J, Sharp, A, and Farrelly, L

Subjects
0301 basic medicine, Oncology, Lung Neoplasms, IMPACT, Biopsy, DNA Mutational Analysis, Drug resistance, Metastasis, 0302 clinical medicine, Limit of Detection, Carcinoma, Non-Small-Cell Lung, Medicine, Neoplasm Metastasis, Early Detection of Cancer, Multidisciplinary, medicine.diagnostic_test, Phylogenetic tree, DNA, Neoplasm, STATISTICS, 3. Good health, Tumor Burden, Multidisciplinary Sciences, Cell Tracking, PEACE consortium, 030220 oncology & carcinogenesis, Disease Progression, Science & Technology - Other Topics, medicine.medical_specialty, CARCINOMA, Tumour heterogeneity, General Science & Technology, Early detection, Evolution, Molecular, 03 medical and health sciences, Internal medicine, MD Multidisciplinary, Carcinoma, Humans, Cell Lineage, Lung cancer, Postoperative Care, Science & Technology, MUTATIONS, TRACERx consortium, business.industry, CIRCULATING TUMOR DNA, Reproducibility of Results, medicine.disease, R1, NEGATIVE BREAST-CANCER, Clone Cells, 030104 developmental biology, Drug Resistance, Neoplasm, UPTAKE RATIO, Immunology, FDG PET, Neoplasm Recurrence, Local, business, Multiplex Polymerase Chain Reaction
Abstract

The early detection of relapse following primary surgery for non-small-cell lung cancer and the characterization of emerging subclones, which seed metastatic sites, might offer new therapeutic approaches for limiting tumour recurrence. The ability to track the evolutionary dynamics of early-stage lung cancer non-invasively in circulating tumour DNA (ctDNA) has not yet been demonstrated. Here we use a tumour-specific phylogenetic approach to profile the ctDNA of the first 100 TRACERx (Tracking Non-Small-Cell Lung Cancer Evolution Through Therapy (Rx)) study participants, including one patient who was also recruited to the PEACE (Posthumous Evaluation of Advanced Cancer Environment) post-mortem study. We identify independent predictors of ctDNA release and analyse the tumour-volume detection limit. Through blinded profiling of postoperative plasma, we observe evidence of adjuvant chemotherapy resistance and identify patients who are very likely to experience recurrence of their lung cancer. Finally, we show that phylogenetic ctDNA profiling tracks the subclonal nature of lung cancer relapse and metastasis, providing a new approach for ctDNA-driven therapeutic studies.

Published
2017

48. Multidimensional resonance analysis of Λc+→ pK−π+

Author

Aitala, E.M., Amato, S., Anjos, J.C., Appel, J.A., Ashery, D., Banerjee, S., Bediaga, I., Blaylock, G., Bracker, S.B., Burchat, P.R., Burnstein, R.A., Carter, T., Carvalho, H.S., Copty, N.K., Cremaldi, L.M., Darling, C., Denisenko, K., Devmal, S., Fernandez, A., Fox, G.F., Gagnon, P., Gobel, C., Gounder, K., Halling, A.M., Herrera, G., Hurvits, G., James, C., Kasper, P.A., Kwan, S., Langs, D.C., Leslie, J., Lundberg, B., Magnin, J., MayTal-Beck, S., Meadows, B., de Mello Neto, J.R.T., Mihalcea, D., Milburn, R.H., de Miranda, J.M., Napier, A., Nguyen, A., d'Oliveira, A.B., O'Shaughnessy, K., Peng, K.C., Perera, L.P., Purohit, M.V., Quinn, B., Radeztsky, S., Rafatian, A., Reay, N.W., Reidy, J.J., dos Reis, A.C., Rubin, H.A., Sanders, D.A., Santha, A.K.S., Santoro, A.F.S., Schwartz, A.J., Sheaff, M., Sidwell, R.A., Slaughter, A.J., Sokoloff, M.D., Solano, J., Stanton, N.R., Stefanski, R.J., Stenson, K., Summers, D.J., Takach, S., Thorne, K., Tripathi, A.K., Watanabe, S., Weiss-Babai, R., Wiener, J., Witchey, N., Wolin, E., Yang, S.M., Yi, D., Yoshida, S., Zaliznyak, R., and Zhang, C.

Published
2000
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