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9. Oncogenic signaling pathways in the Cancer Genome Atlas

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Sanchez-Vega, F., Mina, M., Armenia, J., Chatila, W. K., Luna, A., La, K. C., Dimitriadoy, S., Liu, D. L., Kantheti, H. S., Saghafinia, S., Chakravarty, D., Daian, F., Gao, Q., Bailey, M. H., Liang, W. -W., Foltz, S. M., Shmulevich, I., Ding, L., Heins, Z., Ochoa, A., Gross, B., Gao, J., Zhang, H., Kundra, R., Kandoth, C., Bahceci, I., Dervishi, L., Doğrusöz, Uğur, Zhou, W., Shen, H., Laird, P. W., Way, G. P., Greene, C. S., Liang, H., Xiao, Y., Wang, C., Iavarone, A., Berger, A. H., Bivona, T. G., Lazar, A. J., Hammer, G. D., Giordano, T., Kwong, L. N., McArthur, G., Huang, C., Tward, A. D., Frederick, M. J., McCormick, F., Meyerson, M., Caesar-Johnson, S. J., Demchok, J. A., Felau, I., Kasapi, M., Ferguson, M. L., Hutter, C. M., Sofia, H. J., Tarnuzzer, R., Wang, Z., Yang, L., Zenklusen, J. C., Zhang, J. J., Chudamani, S., Liu, J., Lolla, L., Naresh, R., Pihl, T., Sun, Q., Wan, Y., Wu, Y., Cho, J., DeFreitas, T., Frazer, S., Gehlenborg, N., Getz, G., Heiman, D. I., Kim, J., Lawrence, M. S., Lin, P., Meier, S., Noble, M. S., Saksena, G., Voet, D., Bernard, B., Chambwe, N., Dhankani, V., Knijnenburg, T., Kramer, R., Leinonen, K., Liu, Y., Miller, M., Reynolds, S., Thorsson, V., Zhang, W., Akbani, R., Broom, B. M., Hegde, A. M., Ju, Z., Kanchi, R. S., Korkut, A., Li, J., Ling, S., Liu W., Lu, Y., Mills, G. B., Ng, K. -S., Rao, A., Ryan, M., Wang, J., Weinstein, J. N., Zhang, J., Abeshouse, A., de, Bruijn, I., Gross, B. E., Heins, Z. J., La, K., Ladanyi, M., Nissan, M. G., Phillips, S. M., Reznik, E., Sander, C., Schultz, N., Sheridan, R., Sumer, S. O., Sun, Y., Taylor, B. S., Anur, P., Peto, M., Spellman, P., Benz, C., Stuart, J. M., Wong, C. K., Yau, C., Hayes, D. N., Parker, J. S., Wilkerson, M. D., Ally, A., Balasundaram, M., Bowlby, R., Brooks, D., Carlsen, R., Chuah, E., Dhalla, N., Holt, R., Jones, S. J. M., Kasaian, K., Lee, D., Ma, Y., Marra, M. A., Mayo, M., Moore, R. A., Mungall, A. J., Mungall, K., Robertson, A. G., Sadeghi, S., Schein, J. E., Sipahimalani, P., Tam, A., Thiessen, N., Tse, K., Wong, T., Berger, A. C., Beroukhim, R., Cherniack, A. D., Cibulskis, C., Gabriel, S. B., Gao, G. F., Ha, G., Schumacher, S. E., Shih, J., Kucherlapati, M. H., Kucherlapati, R. S., Baylin, S., Cope, L., Danilova, L., Bootwalla, M. S., Lai, P. H., Maglinte, D. T., Van, Den, Berg, D. J., Weisenberger, D. J., Auman, J. T., Balu, S., Bodenheimer, T., Fan, C., Hoadley, K. A., Hoyle, A. P., Jefferys, S. R., Jones, C. D., Meng, S., Mieczkowski, P. A., Mose, L. E., Perou, A. H., Perou, C. M., Roach, J., Shi, Y., Simons, J. V., Skelly, T., Soloway, M. G., Tan, D., Veluvolu, U., Fan, H., Hinoue, T., Bellair, M., Chang, K., Covington, K., Creighton, C. J., Dinh, H., Doddapaneni, H., Donehower, L. A., Drummond, J., Gibbs, R. A., Glenn, R., Hale, W., Han, Y., Hu, J., Korchina, V., Lee, S., Lewis, L., Li, W., Liu, X., Morgan, M., Morton, D., Muzny, D., Santibanez, J., Sheth, M., Shinbrot, E., Wang, L., Wang, M., Wheeler, D. A., Xi, L., Zhao, F., Hess, J., Appelbaum, E. L., Bailey, M., Cordes, M. G., Fronick, C. C., Fulton, L. A., Fulton, R. S., Mardis, E. R., McLellan, M. D., Miller, C. A., Schmidt, H. K., Wilson, R. K., Crain, D., Curley, E., Gardner, J., Lau, K., Mallery, D., Morris, S., Paulauskis, J., Penny, R., Shelton, C., Shelton, T., Sherman, M., Thompson, E., Yena, P., Bowen, J., Gastier-Foster, J. M., Gerken, M., Leraas, K. M., Lichtenberg, T. M., Ramirez, N. C., Wise, L., Zmuda, E., Corcoran, N., Costello, T., Hovens, C., Carvalho, A. L., de, Carvalho, A. C., Fregnani, J. H., Longatto-Filho, A., Reis, R. M., Scapulatempo-Neto, C., Silveira, H. C. S., Vidal, D. O., Burnette, A., Eschbacher, J., Hermes, B., Noss, A., Singh, R., Anderson, M. L., Castro, P. D., Ittmann, M., Huntsman, D., Kohl, B., Le, X., Thorp, R., Andry, C., Duffy, E. R., Lyadov, V., Paklina, O., Setdikova, G., Shabunin, A., Tavobilov, M., McPherson, C., Warnick, R., Berkowitz, R., Cramer, D., Feltmate, C., Horowitz, N., Kibel, A., Muto, M., Raut, C. P., Malykh, A., Barnholtz-Sloan, J. S., Barrett, W., Devine, K., Fulop, J., Ostrom, Q. T., Shimmel, K., Wolinsky, Y., Sloan, A. E., De, Rose, A., Giuliante, F., Goodman, M., Karlan, B. Y., Hagedorn, C. H., Eckman, J., Harr, J., Myers, J., Tucker, K., Zach, L. A., Deyarmin, B., Hu, H., Kvecher, L., Larson, C., Mural, R. J., Somiari, S., Vicha, A., Zelinka, T., Bennett, J., Iacocca, M., Rabeno, B., Swanson, P., Latour, M., Lacombe, L., Têtu, B., Bergeron, A., McGraw, M., Staugaitis, S. M., Chabot, J., Hibshoosh, H., Sepulveda, A., Su, T., Wang, T., Potapova, O., Voronina, O., Desjardins, L., Mariani, O., Roman-Roman, S., Sastre, X., Stern, M. -H., Cheng, F., Signoretti, S., Berchuck, A., Bigner, D., Lipp, E., Marks, J., McCall, S., McLendon, R., Secord, A., Sharp, A., Behera, M., Brat, D. J., Chen, A., Delman, K., Force, S., Khuri, F., Magliocca, K., Maithel, S., Olson, J. J., Owonikoko, T., Pickens, A., Ramalingam, S., Shin, D. M., Sica, G., Van, Meir, E. G., Eijckenboom, W., Gillis, A., Korpershoek, E., Looijenga, L., Oosterhuis, W., Stoop, H., van, Kessel, K. E., Zwarthoff, E. C., Calatozzolo, C., Cuppini, L., Cuzzubbo, S., DiMeco, F., Finocchiaro, G., Mattei, L., Perin, A., Pollo, B., Chen, C., Houck, J., Lohavanichbutr, P., Hartmann, A., Stoehr, C., Stoehr, R., Taubert, H., Wach, S., Wullich, B., Kycler, W., Murawa, D., Wiznerowicz, M., Chung, K., Edenfield, W. J., Martin, J., Baudin, E., Bubley, G., Bueno, R., De, Rienzo, A., Richards, W. G., Kalkanis, S., Mikkelsen, T., Noushmehr, H., Scarpace, L., Girard, N., Aymerich, M., Campo, E., Giné, E., Guillermo, A. L., Van, Bang, N., Hanh, P. T., Phu, B. D., Tang, Y., Colman, H., Evason, K., Dottino, P. R., Martignetti, J. A., Gabra, H., Juhl, H., Akeredolu, T., Stepa, S., Hoon, D., Ahn, K., Kang, K. J., Beuschlein, F., Breggia, A., Birrer, M., Bell, D., Borad, M., Bryce, A. H., Castle, E., Chandan, V., Cheville, J., Copland, J. A., Farnell, M., Flotte, T., Giama, N., Ho, T., Kendrick, M., Kocher, J. -P., Kopp, K., Moser, C., Nagorney, D., O'Brien, D., O'Neill, B. P., Patel, T., Petersen, G., Que, F., Rivera, M., Roberts, L., Smallridge, R., Smyrk, T., Stanton, M., Thompson, R. H., Torbenson, M., Yang, J. D., Zhang, L., Brimo, F., Ajani, J. A., Gonzalez, A. M. A., Behrens, C., Bondaruk, J., Broaddus, R., Czerniak, B., Esmaeli, B., Fujimoto, J., Gershenwald, J., Guo, C., Logothetis, C., Meric-Bernstam, F., Moran, C., Ramondetta, L., Rice, D., Sood, A., Tamboli, P., Thompson, T., Troncoso, P., Tsao, A., Wistuba, I., Carter, C., Haydu, L., Hersey, P., Jakrot, V., Kakavand, H., Kefford, R., Lee, K., Long, G., Mann, G., Quinn, M., Saw, R., Scolyer, R., Shannon, K., Spillane, A., Stretch, J., Synott, M., Thompson, J., Wilmott, J., Al-Ahmadie, H., Chan, T. A., Ghossein, R., Gopalan, A., Levine, D. A., Reuter, V., Singer, S., Singh, B., Tien, N. V., Broudy, T., Mirsaidi, C., Nair, P., Drwiega, P., Miller, J., Smith, J., Zaren, H., Park, J. -W., Hung, N. P., Kebebew, E., Linehan, W. M., Metwalli, A. R., Pacak, K., Pinto, P. A., Schiffman, M., Schmidt, L. S., Vocke, C. D., Wentzensen, N., Worrell, R., Yang, H., Moncrieff, M., Goparaju, C., Melamed, J., Pass, H., Botnariuc, N., Caraman, I., Cernat, M., Chemencedji, I., Clipca, A., Doruc, S., Gorincioi, G., Mura, S., Pirtac, M., Stancul, I., Tcaciuc, D., Albert, M., Alexopoulou, I., Arnaout, A., Bartlett, J., Engel, J., Gilbert, S., Parfitt, J., Sekhon, H., Thomas, G., Rassl, D. M., Rintoul, R. C., Bifulco, C., Tamakawa, R., Urba, W., Hayward, N., Timmers, H., Antenucci, A., Facciolo, F., Grazi, G., Marino, M., Merola, R., de, Krijger, R., Gimenez-Roqueplo, A. -P., Piché, A., Chevalier, S., McKercher, G., Birsoy, K., Barnett, G., Brewer, C., Farver, C., Naska, T., Pennell, N. A., Raymond, D., Schilero, C., Smolenski, K., Williams, F., Morrison, C., Borgia, J. A., Liptay, M. J., Pool, M., Seder, C. W., Junker, K., Omberg, L., Dinkin, M., Manikhas, G., Alvaro, D., Bragazzi, M. C., Cardinale, V., Carpino, G., Gaudio, E., Chesla, D., Cottingham, S., Dubina, M., Moiseenko, F., Dhanasekaran, R., Becker, K. -F., Janssen, K. -P., Slotta-Huspenina, J., Abdel-Rahman, M. H., Aziz, D., Bell, S., Cebulla, C. M., Davis, A., Duell, R., Elder, J. B., Hilty, J., Kumar, B., Lang, J., Lehman, N. L., Mandt, R., Nguyen, P., Pilarski, R., Rai, K., Schoenfield, L., Senecal, K., Wakely, P., Hansen, P., Lechan, R., Powers, J., Tischler, A., Grizzle, W. E., Sexton, K. C., Kastl, A., Henderson, J., Porten, S., Waldmann, J., Fassnacht, M., Asa, S. L., Schadendorf, D., Couce, M., Graefen, M., Huland, H., Sauter, G., Schlomm, T., Simon, R., Tennstedt, P., Olabode, O., Nelson, M., Bathe, O., Carroll, P. R., Chan, J. M., Disaia, P., Glenn, P., Kelley, R. K., Landen, C. N., Phillips, J., Prados, M., Simko, J., Smith-McCune, K., VandenBerg, S., Roggin, K., Fehrenbach, A., Kendler, A., Sifri, S., Steele, R., Jimeno, A., Carey, F., Forgie, I., Mannelli, M., Carney, M., Hernandez, B., Campos, B., Herold-Mende, C., Jungk, C., Unterberg, A., von, Deimling, A., Bossler, A., Galbraith, J., Jacobus, L., Knudson, M., Knutson, T., Ma, D., Milhem, M., Sigmund, R., Godwin, A. K., Madan, R., Rosenthal, H. G., Adebamowo, C., Adebamowo, S. N., Boussioutas, A., Beer, D., Mes-Masson, A. -M., Saad, F., Bocklage, T., Landrum, L., Mannel, R., Moore, K., Moxley, K., Postier, R., Walker, J., Zuna, R., Feldman, M., Valdivieso, F., Dhir, R., Luketich, J., Pinero, E. M. M., Quintero-Aguilo, M., Carlotti, C. G., Jr., Dos, Santos, J. S., Kemp, R., Sankarankuty, A., Tirapelli, D., Catto, J., Agnew, K., Swisher, E., Creaney, J., Robinson, B., Shelley, C. S., Godwin, E. M., Kendall, S., Shipman, C., Bradford, C., Carey, T., Haddad, A., Moyer, J., Peterson, L., Prince, M., Rozek, L., Wolf, G., Bowman, R., Fong, K. M., Yang, I., Korst, R., Rathmell, W. K., Fantacone-Campbell, J. L., Hooke, J. A., Kovatich, A. J., Shriver, C. D., DiPersio, J., Drake, B., Govindan, R., Heath, S., Ley, T., Van, Tine, B., Westervelt, P., Rubin, M. A., Lee, J. I., Aredes, N. D., Mariamidze, A., Van, Allen, E. M., Ciriello, G., The, Cancer, Genome, Atlas, Research, Network.tif, Doğrusöz, Uğur, Cancer Genome Atlas Research Network, Caesar-Johnson, S.J., Demchok, J.A., Felau, I., Kasapi, M., Ferguson, M.L., Hutter, C.M., Sofia, H.J., Tarnuzzer, R., Wang, Z., Yang, L., Zenklusen, J.C., Zhang, J.J., Chudamani, S., Liu, J., Lolla, L., Naresh, R., Pihl, T., Sun, Q., Wan, Y., Wu, Y., Cho, J., DeFreitas, T., Frazer, S., Gehlenborg, N., Getz, G., Heiman, D.I., Kim, J., Lawrence, M.S., Lin, P., Meier, S., Noble, M.S., Saksena, G., Voet, D., Zhang, H., Bernard, B., Chambwe, N., Dhankani, V., Knijnenburg, T., Kramer, R., Leinonen, K., Liu, Y., Miller, M., Reynolds, S., Shmulevich, I., Thorsson, V., Zhang, W., Akbani, R., Broom, B.M., Hegde, A.M., Ju, Z., Kanchi, R.S., Korkut, A., Li, J., Liang, H., Ling, S., Liu, W., Lu, Y., Mills, G.B., Ng, K.S., Rao, A., Ryan, M., Wang, J., Weinstein, J.N., Zhang, J., Abeshouse, A., Armenia, J., Chakravarty, D., Chatila, W.K., de Bruijn, I., Gao, J., Gross, B.E., Heins, Z.J., Kundra, R., La, K., Ladanyi, M., Luna, A., Nissan, M.G., Ochoa, A., Phillips, S.M., Reznik, E., Sanchez-Vega, F., Sander, C., Schultz, N., Sheridan, R., Sumer, S.O., Sun, Y., Taylor, B.S., Anur, P., Peto, M., Spellman, P., Benz, C., Stuart, J.M., Wong, C.K., Yau, C., Hayes, D.N., Parker, J.S., Wilkerson, M.D., Ally, A., Balasundaram, M., Bowlby, R., Brooks, D., Carlsen, R., Chuah, E., Dhalla, N., Holt, R., Jones, SJM, Kasaian, K., Lee, D., Ma, Y., Marra, M.A., Mayo, M., Moore, R.A., Mungall, A.J., Mungall, K., Robertson, A.G., Sadeghi, S., Schein, J.E., Sipahimalani, P., Tam, A., Thiessen, N., Tse, K., Wong, T., Berger, A.C., Beroukhim, R., Cherniack, A.D., Cibulskis, C., Gabriel, S.B., Gao, G.F., Ha, G., Meyerson, M., Schumacher, S.E., Shih, J., Kucherlapati, M.H., Kucherlapati, R.S., Baylin, S., Cope, L., Danilova, L., Bootwalla, M.S., Lai, P.H., Maglinte, D.T., Van Den Berg, D.J., Weisenberger, D.J., Auman, J.T., Balu, S., Bodenheimer, T., Fan, C., Hoadley, K.A., Hoyle, A.P., Jefferys, S.R., Jones, C.D., Meng, S., Mieczkowski, P.A., Mose, L.E., Perou, A.H., Perou, C.M., Roach, J., Shi, Y., Simons, J.V., Skelly, T., Soloway, M.G., Tan, D., Veluvolu, U., Fan, H., Hinoue, T., Laird, P.W., Shen, H., Zhou, W., Bellair, M., Chang, K., Covington, K., Creighton, C.J., Dinh, H., Doddapaneni, H., Donehower, L.A., Drummond, J., Gibbs, R.A., Glenn, R., Hale, W., Han, Y., Hu, J., Korchina, V., Lee, S., Lewis, L., Li, W., Liu, X., Morgan, M., Morton, D., Muzny, D., Santibanez, J., Sheth, M., Shinbrot, E., Wang, L., Wang, M., Wheeler, D.A., Xi, L., Zhao, F., Hess, J., Appelbaum, E.L., Bailey, M., Cordes, M.G., Ding, L., Fronick, C.C., Fulton, L.A., Fulton, R.S., Kandoth, C., Mardis, E.R., McLellan, M.D., Miller, C.A., Schmidt, H.K., Wilson, R.K., Crain, D., Curley, E., Gardner, J., Lau, K., Mallery, D., Morris, S., Paulauskis, J., Penny, R., Shelton, C., Shelton, T., Sherman, M., Thompson, E., Yena, P., Bowen, J., Gastier-Foster, J.M., Gerken, M., Leraas, K.M., Lichtenberg, T.M., Ramirez, N.C., Wise, L., Zmuda, E., Corcoran, N., Costello, T., Hovens, C., Carvalho, A.L., de Carvalho, A.C., Fregnani, J.H., Longatto-Filho, A., Reis, R.M., Scapulatempo-Neto, C., Silveira, HCS, Vidal, D.O., Burnette, A., Eschbacher, J., Hermes, B., Noss, A., Singh, R., Anderson, M.L., Castro, P.D., Ittmann, M., Huntsman, D., Kohl, B., Le, X., Thorp, R., Andry, C., Duffy, E.R., Lyadov, V., Paklina, O., Setdikova, G., Shabunin, A., Tavobilov, M., McPherson, C., Warnick, R., Berkowitz, R., Cramer, D., Feltmate, C., Horowitz, N., Kibel, A., Muto, M., Raut, C.P., Malykh, A., Barnholtz-Sloan, J.S., Barrett, W., Devine, K., Fulop, J., Ostrom, Q.T., Shimmel, K., Wolinsky, Y., Sloan, A.E., De Rose, A., Giuliante, F., Goodman, M., Karlan, B.Y., Hagedorn, C.H., Eckman, J., Harr, J., Myers, J., Tucker, K., Zach, L.A., Deyarmin, B., Hu, H., Kvecher, L., Larson, C., Mural, R.J., Somiari, S., Vicha, A., Zelinka, T., Bennett, J., Iacocca, M., Rabeno, B., Swanson, P., Latour, M., Lacombe, L., Têtu, B., Bergeron, A., McGraw, M., Staugaitis, S.M., Chabot, J., Hibshoosh, H., Sepulveda, A., Su, T., Wang, T., Potapova, O., Voronina, O., Desjardins, L., Mariani, O., Roman-Roman, S., Sastre, X., Stern, M.H., Cheng, F., Signoretti, S., Berchuck, A., Bigner, D., Lipp, E., Marks, J., McCall, S., McLendon, R., Secord, A., Sharp, A., Behera, M., Brat, D.J., Chen, A., Delman, K., Force, S., Khuri, F., Magliocca, K., Maithel, S., Olson, J.J., Owonikoko, T., Pickens, A., Ramalingam, S., Shin, D.M., Sica, G., Van Meir, E.G., Eijckenboom, W., Gillis, A., Korpershoek, E., Looijenga, L., Oosterhuis, W., Stoop, H., van Kessel, K.E., Zwarthoff, E.C., Calatozzolo, C., Cuppini, L., Cuzzubbo, S., DiMeco, F., Finocchiaro, G., Mattei, L., Perin, A., Pollo, B., Chen, C., Houck, J., Lohavanichbutr, P., Hartmann, A., Stoehr, C., Stoehr, R., Taubert, H., Wach, S., Wullich, B., Kycler, W., Murawa, D., Wiznerowicz, M., Chung, K., Edenfield, W.J., Martin, J., Baudin, E., Bubley, G., Bueno, R., De Rienzo, A., Richards, W.G., Kalkanis, S., Mikkelsen, T., Noushmehr, H., Scarpace, L., Girard, N., Aymerich, M., Campo, E., Giné, E., Guillermo, A.L., Van Bang, N., Hanh, P.T., Phu, B.D., Tang, Y., Colman, H., Evason, K., Dottino, P.R., Martignetti, J.A., Gabra, H., Juhl, H., Akeredolu, T., Stepa, S., Hoon, D., Ahn, K., Kang, K.J., Beuschlein, F., Breggia, A., Birrer, M., Bell, D., Borad, M., Bryce, A.H., Castle, E., Chandan, V., Cheville, J., Copland, J.A., Farnell, M., Flotte, T., Giama, N., Ho, T., Kendrick, M., Kocher, J.P., Kopp, K., Moser, C., Nagorney, D., O'Brien, D., O'Neill, B.P., Patel, T., Petersen, G., Que, F., Rivera, M., Roberts, L., Smallridge, R., Smyrk, T., Stanton, M., Thompson, R.H., Torbenson, M., Yang, J.D., Zhang, L., Brimo, F., Ajani, J.A., Gonzalez, AMA, Behrens, C., Bondaruk, J., Broaddus, R., Czerniak, B., Esmaeli, B., Fujimoto, J., Gershenwald, J., Guo, C., Lazar, A.J., Logothetis, C., Meric-Bernstam, F., Moran, C., Ramondetta, L., Rice, D., Sood, A., Tamboli, P., Thompson, T., Troncoso, P., Tsao, A., Wistuba, I., Carter, C., Haydu, L., Hersey, P., Jakrot, V., Kakavand, H., Kefford, R., Lee, K., Long, G., Mann, G., Quinn, M., Saw, R., Scolyer, R., Shannon, K., Spillane, A., Stretch, J., Synott, M., Thompson, J., Wilmott, J., Al-Ahmadie, H., Chan, T.A., Ghossein, R., Gopalan, A., Levine, D.A., Reuter, V., Singer, S., Singh, B., Tien, N.V., Broudy, T., Mirsaidi, C., Nair, P., Drwiega, P., Miller, J., Smith, J., Zaren, H., Park, J.W., Hung, N.P., Kebebew, E., Linehan, W.M., Metwalli, A.R., Pacak, K., Pinto, P.A., Schiffman, M., Schmidt, L.S., Vocke, C.D., Wentzensen, N., Worrell, R., Yang, H., Moncrieff, M., Goparaju, C., Melamed, J., Pass, H., Botnariuc, N., Caraman, I., Cernat, M., Chemencedji, I., Clipca, A., Doruc, S., Gorincioi, G., Mura, S., Pirtac, M., Stancul, I., Tcaciuc, D., Albert, M., Alexopoulou, I., Arnaout, A., Bartlett, J., Engel, J., Gilbert, S., Parfitt, J., Sekhon, H., Thomas, G., Rassl, D.M., Rintoul, R.C., Bifulco, C., Tamakawa, R., Urba, W., Hayward, N., Timmers, H., Antenucci, A., Facciolo, F., Grazi, G., Marino, M., Merola, R., de Krijger, R., Gimenez-Roqueplo, A.P., Piché, A., Chevalier, S., McKercher, G., Birsoy, K., Barnett, G., Brewer, C., Farver, C., Naska, T., Pennell, N.A., Raymond, D., Schilero, C., Smolenski, K., Williams, F., Morrison, C., Borgia, J.A., Liptay, M.J., Pool, M., Seder, C.W., Junker, K., Omberg, L., Dinkin, M., Manikhas, G., Alvaro, D., Bragazzi, M.C., Cardinale, V., Carpino, G., Gaudio, E., Chesla, D., Cottingham, S., Dubina, M., Moiseenko, F., Dhanasekaran, R., Becker, K.F., Janssen, K.P., Slotta-Huspenina, J., Abdel-Rahman, M.H., Aziz, D., Bell, S., Cebulla, C.M., Davis, A., Duell, R., Elder, J.B., Hilty, J., Kumar, B., Lang, J., Lehman, N.L., Mandt, R., Nguyen, P., Pilarski, R., Rai, K., Schoenfield, L., Senecal, K., Wakely, P., Hansen, P., Lechan, R., Powers, J., Tischler, A., Grizzle, W.E., Sexton, K.C., Kastl, A., Henderson, J., Porten, S., Waldmann, J., Fassnacht, M., Asa, S.L., Schadendorf, D., Couce, M., Graefen, M., Huland, H., Sauter, G., Schlomm, T., Simon, R., Tennstedt, P., Olabode, O., Nelson, M., Bathe, O., Carroll, P.R., Chan, J.M., Disaia, P., Glenn, P., Kelley, R.K., Landen, C.N., Phillips, J., Prados, M., Simko, J., Smith-McCune, K., VandenBerg, S., Roggin, K., Fehrenbach, A., Kendler, A., Sifri, S., Steele, R., Jimeno, A., Carey, F., Forgie, I., Mannelli, M., Carney, M., Hernandez, B., Campos, B., Herold-Mende, C., Jungk, C., Unterberg, A., von Deimling, A., Bossler, A., Galbraith, J., Jacobus, L., Knudson, M., Knutson, T., Ma, D., Milhem, M., Sigmund, R., Godwin, A.K., Madan, R., Rosenthal, H.G., Adebamowo, C., Adebamowo, S.N., Boussioutas, A., Beer, D., Giordano, T., Mes-Masson, A.M., Saad, F., Bocklage, T., Landrum, L., Mannel, R., Moore, K., Moxley, K., Postier, R., Walker, J., Zuna, R., Feldman, M., Valdivieso, F., Dhir, R., Luketich, J., Pinero, EMM, Quintero-Aguilo, M., Carlotti, C.G., Dos Santos, J.S., Kemp, R., Sankarankuty, A., Tirapelli, D., Catto, J., Agnew, K., Swisher, E., Creaney, J., Robinson, B., Shelley, C.S., Godwin, E.M., Kendall, S., Shipman, C., Bradford, C., Carey, T., Haddad, A., Moyer, J., Peterson, L., Prince, M., Rozek, L., Wolf, G., Bowman, R., Fong, K.M., Yang, I., Korst, R., Rathmell, W.K., Fantacone-Campbell, J.L., Hooke, J.A., Kovatich, A.J., Shriver, C.D., DiPersio, J., Drake, B., Govindan, R., Heath, S., Ley, T., Van Tine, B., Westervelt, P., Rubin, M.A., Lee, J.I., Aredes, N.D., Mariamidze, A., SAIC-F-Frederick, Inc, Leidos Biomedical Research, Inc., Sanchez-Vega F., Mina M., Armenia J., Chatila W.K., Luna A., La K.C., Dimitriadoy S., Liu D.L., Kantheti H.S., Saghafinia S., Chakravarty D., Daian F., Gao Q., Bailey M.H., Liang W.-W., Foltz S.M., Shmulevich I., Ding L., Heins Z., Ochoa A., Gross B., Gao J., Zhang H., Kundra R., Kandoth C., Bahceci I., Dervishi L., Dogrusoz U., Zhou W., Shen H., Laird P.W., Way G.P., Greene C.S., Liang H., Xiao Y., Wang C., Iavarone A., Berger A.H., Bivona T.G., Lazar A.J., Hammer G.D., Giordano T., Kwong L.N., McArthur G., Huang C., Tward A.D., Frederick M.J., McCormick F., Meyerson M., Caesar-Johnson S.J., Demchok J.A., Felau I., Kasapi M., Ferguson M.L., Hutter C.M., Sofia H.J., Tarnuzzer R., Wang Z., Yang L., Zenklusen J.C., Zhang J.J., Chudamani S., Liu J., Lolla L., Naresh R., Pihl T., Sun Q., Wan Y., Wu Y., Cho J., DeFreitas T., Frazer S., Gehlenborg N., Getz G., Heiman D.I., Kim J., Lawrence M.S., Lin P., Meier S., Noble M.S., Saksena G., Voet D., Bernard B., Chambwe N., Dhankani V., Knijnenburg T., Kramer R., Leinonen K., Liu Y., Miller M., Reynolds S., Thorsson V., Zhang W., Akbani R., Broom B.M., Hegde A.M., Ju Z., Kanchi R.S., Korkut A., Li J., Ling S., Liu W., Lu Y., Mills G.B., Ng K.-S., Rao A., Ryan M., Wang J., Weinstein J.N., Zhang J., Abeshouse A., de Bruijn I., Gross B.E., Heins Z.J., La K., Ladanyi M., Nissan M.G., Phillips S.M., Reznik E., Sander C., Schultz N., Sheridan R., Sumer S.O., Sun Y., Taylor B.S., Anur P., Peto M., Spellman P., Benz C., Stuart J.M., Wong C.K., Yau C., Hayes D.N., Parker J.S., Wilkerson M.D., Ally A., Balasundaram M., Bowlby R., Brooks D., Carlsen R., Chuah E., Dhalla N., Holt R., Jones S.J.M., Kasaian K., Lee D., Ma Y., Marra M.A., Mayo M., Moore R.A., Mungall A.J., Mungall K., Robertson A.G., Sadeghi S., Schein J.E., Sipahimalani P., Tam A., Thiessen N., Tse K., Wong T., Berger A.C., Beroukhim R., Cherniack A.D., Cibulskis C., Gabriel S.B., Gao G.F., Ha G., Schumacher S.E., Shih J., Kucherlapati M.H., Kucherlapati R.S., Baylin S., Cope L., Danilova L., Bootwalla M.S., Lai P.H., Maglinte D.T., Van Den Berg D.J., Weisenberger D.J., Auman J.T., Balu S., Bodenheimer T., Fan C., Hoadley K.A., Hoyle A.P., Jefferys S.R., Jones C.D., Meng S., Mieczkowski P.A., Mose L.E., Perou A.H., Perou C.M., Roach J., Shi Y., Simons J.V., Skelly T., Soloway M.G., Tan D., Veluvolu U., Fan H., Hinoue T., Bellair M., Chang K., Covington K., Creighton C.J., Dinh H., Doddapaneni H., Donehower L.A., Drummond J., Gibbs R.A., Glenn R., Hale W., Han Y., Hu J., Korchina V., Lee S., Lewis L., Li W., Liu X., Morgan M., Morton D., Muzny D., Santibanez J., Sheth M., Shinbrot E., Wang L., Wang M., Wheeler D.A., Xi L., Zhao F., Hess J., Appelbaum E.L., Bailey M., Cordes M.G., Fronick C.C., Fulton L.A., Fulton R.S., Mardis E.R., McLellan M.D., Miller C.A., Schmidt H.K., Wilson R.K., Crain D., Curley E., Gardner J., Lau K., Mallery D., Morris S., Paulauskis J., Penny R., Shelton C., Shelton T., Sherman M., Thompson E., Yena P., Bowen J., Gastier-Foster J.M., Gerken M., Leraas K.M., Lichtenberg T.M., Ramirez N.C., Wise L., Zmuda E., Corcoran N., Costello T., Hovens C., Carvalho A.L., de Carvalho A.C., Fregnani J.H., Longatto-Filho A., Reis R.M., Scapulatempo-Neto C., Silveira H.C.S., Vidal D.O., Burnette A., Eschbacher J., Hermes B., Noss A., Singh R., Anderson M.L., Castro P.D., Ittmann M., Huntsman D., Kohl B., Le X., Thorp R., Andry C., Duffy E.R., Lyadov V., Paklina O., Setdikova G., Shabunin A., Tavobilov M., McPherson C., Warnick R., Berkowitz R., Cramer D., Feltmate C., Horowitz N., Kibel A., Muto M., Raut C.P., Malykh A., Barnholtz-Sloan J.S., Barrett W., Devine K., Fulop J., Ostrom Q.T., Shimmel K., Wolinsky Y., Sloan A.E., De Rose A., Giuliante F., Goodman M., Karlan B.Y., Hagedorn C.H., Eckman J., Harr J., Myers J., Tucker K., Zach L.A., Deyarmin B., Hu H., Kvecher L., Larson C., Mural R.J., Somiari S., Vicha A., Zelinka T., Bennett J., Iacocca M., Rabeno B., Swanson P., Latour M., Lacombe L., Tetu B., Bergeron A., McGraw M., Staugaitis S.M., Chabot J., Hibshoosh H., Sepulveda A., Su T., Wang T., Potapova O., Voronina O., Desjardins L., Mariani O., Roman-Roman S., Sastre X., Stern M.-H., Cheng F., Signoretti S., Berchuck A., Bigner D., Lipp E., Marks J., McCall S., McLendon R., Secord A., Sharp A., Behera M., Brat D.J., Chen A., Delman K., Force S., Khuri F., Magliocca K., Maithel S., Olson J.J., Owonikoko T., Pickens A., Ramalingam S., Shin D.M., Sica G., Van Meir E.G., Eijckenboom W., Gillis A., Korpershoek E., Looijenga L., Oosterhuis W., Stoop H., van Kessel K.E., Zwarthoff E.C., Calatozzolo C., Cuppini L., Cuzzubbo S., DiMeco F., Finocchiaro G., Mattei L., Perin A., Pollo B., Chen C., Houck J., Lohavanichbutr P., Hartmann A., Stoehr C., Stoehr R., Taubert H., Wach S., Wullich B., Kycler W., Murawa D., Wiznerowicz M., Chung K., Edenfield W.J., Martin J., Baudin E., Bubley G., Bueno R., De Rienzo A., Richards W.G., Kalkanis S., Mikkelsen T., Noushmehr H., Scarpace L., Girard N., Aymerich M., Campo E., Gine E., Guillermo A.L., Van Bang N., Hanh P.T., Phu B.D., Tang Y., Colman H., Evason K., Dottino P.R., Martignetti J.A., Gabra H., Juhl H., Akeredolu T., Stepa S., Hoon D., Ahn K., Kang K.J., Beuschlein F., Breggia A., Birrer M., Bell D., Borad M., Bryce A.H., Castle E., Chandan V., Cheville J., Copland J.A., Farnell M., Flotte T., Giama N., Ho T., Kendrick M., Kocher J.-P., Kopp K., Moser C., Nagorney D., O'Brien D., O'Neill B.P., Patel T., Petersen G., Que F., Rivera M., Roberts L., Smallridge R., Smyrk T., Stanton M., Thompson R.H., Torbenson M., Yang J.D., Zhang L., Brimo F., Ajani J.A., Gonzalez A.M.A., Behrens C., Bondaruk J., Broaddus R., Czerniak B., Esmaeli B., Fujimoto J., Gershenwald J., Guo C., Logothetis C., Meric-Bernstam F., Moran C., Ramondetta L., Rice D., Sood A., Tamboli P., Thompson T., Troncoso P., Tsao A., Wistuba I., Carter C., Haydu L., Hersey P., Jakrot V., Kakavand H., Kefford R., Lee K., Long G., Mann G., Quinn M., Saw R., Scolyer R., Shannon K., Spillane A., Stretch J., Synott M., Thompson J., Wilmott J., Al-Ahmadie H., Chan T.A., Ghossein R., Gopalan A., Levine D.A., Reuter V., Singer S., Singh B., Tien N.V., Broudy T., Mirsaidi C., Nair P., Drwiega P., Miller J., Smith J., Zaren H., Park J.-W., Hung N.P., Kebebew E., Linehan W.M., Metwalli A.R., Pacak K., Pinto P.A., Schiffman M., Schmidt L.S., Vocke C.D., Wentzensen N., Worrell R., Yang H., Moncrieff M., Goparaju C., Melamed J., Pass H., Botnariuc N., Caraman I., Cernat M., Chemencedji I., Clipca A., Doruc S., Gorincioi G., Mura S., Pirtac M., Stancul I., Tcaciuc D., Albert M., Alexopoulou I., Arnaout A., Bartlett J., Engel J., Gilbert S., Parfitt J., Sekhon H., Thomas G., Rassl D.M., Rintoul R.C., Bifulco C., Tamakawa R., Urba W., Hayward N., Timmers H., Antenucci A., Facciolo F., Grazi G., Marino M., Merola R., de Krijger R., Gimenez-Roqueplo A.-P., Piche A., Chevalier S., McKercher G., Birsoy K., Barnett G., Brewer C., Farver C., Naska T., Pennell N.A., Raymond D., Schilero C., Smolenski K., Williams F., Morrison C., Borgia J.A., Liptay M.J., Pool M., Seder C.W., Junker K., Omberg L., Dinkin M., Manikhas G., Alvaro D., Bragazzi M.C., Cardinale V., Carpino G., Gaudio E., Chesla D., Cottingham S., Dubina M., Moiseenko F., Dhanasekaran R., Becker K.-F., Janssen K.-P., Slotta-Huspenina J., Abdel-Rahman M.H., Aziz D., Bell S., Cebulla C.M., Davis A., Duell R., Elder J.B., Hilty J., Kumar B., Lang J., Lehman N.L., Mandt R., Nguyen P., Pilarski R., Rai K., Schoenfield L., Senecal K., Wakely P., Hansen P., Lechan R., Powers J., Tischler A., Grizzle W.E., Sexton K.C., Kastl A., Henderson J., Porten S., Waldmann J., Fassnacht M., Asa S.L., Schadendorf D., Couce M., Graefen M., Huland H., Sauter G., Schlomm T., Simon R., Tennstedt P., Olabode O., Nelson M., Bathe O., Carroll P.R., Chan J.M., Disaia P., Glenn P., Kelley R.K., Landen C.N., Phillips J., Prados M., Simko J., Smith-McCune K., VandenBerg S., Roggin K., Fehrenbach A., Kendler A., Sifri S., Steele R., Jimeno A., Carey F., Forgie I., Mannelli M., Carney M., Hernandez B., Campos B., Herold-Mende C., Jungk C., Unterberg A., von Deimling A., Bossler A., Galbraith J., Jacobus L., Knudson M., Knutson T., Ma D., Milhem M., Sigmund R., Godwin A.K., Madan R., Rosenthal H.G., Adebamowo C., Adebamowo S.N., Boussioutas A., Beer D., Mes-Masson A.-M., Saad F., Bocklage T., Landrum L., Mannel R., Moore K., Moxley K., Postier R., Walker J., Zuna R., Feldman M., Valdivieso F., Dhir R., Luketich J., Pinero E.M.M., Quintero-Aguilo M., Carlotti C.G., Dos Santos J.S., Kemp R., Sankarankuty A., Tirapelli D., Catto J., Agnew K., Swisher E., Creaney J., Robinson B., Shelley C.S., Godwin E.M., Kendall S., Shipman C., Bradford C., Carey T., Haddad A., Moyer J., Peterson L., Prince M., Rozek L., Wolf G., Bowman R., Fong K.M., Yang I., Korst R., Rathmell W.K., Fantacone-Campbell J.L., Hooke J.A., Kovatich A.J., Shriver C.D., DiPersio J., Drake B., Govindan R., Heath S., Ley T., Van Tine B., Westervelt P., Rubin M.A., Lee J.I., Aredes N.D., Mariamidze A., Van Allen E.M., and Ciriello G.

Subjects
0301 basic medicine, cancer genome atlas, cancer genomics, combination therapy, pan-cancer, PanCanAtlas, precision oncology, signaling pathways, TCGA, therapeutics, whole exome sequencing, Signaling pathways, Somatic cell, Wnt Protein, Cancer Genome Atlas Research Network, Biochemistry, Medical and Health Sciences, Phosphatidylinositol 3-Kinases, Transforming Growth Factor beta, Neoplasms, Databases, Genetic, LS2_1, Cancer genomics, LS4_6, 610 Medicine & health, 11 Medical and Health Sciences, Cancer, biology, Wnt signaling pathway, cancer genomic, Precision oncology, Biological Sciences, Cell cycle, DNA methylation, Signal transduction, CICLO CELULAR, Life Sciences & Biomedicine, Genes, Neoplasm, Humans, Neoplasms/genetics, Neoplasms/pathology, Phosphatidylinositol 3-Kinases/genetics, Phosphatidylinositol 3-Kinases/metabolism, Signal Transduction/genetics, Transforming Growth Factor beta/genetics, Transforming Growth Factor beta/metabolism, Tumor Suppressor Protein p53/genetics, Tumor Suppressor Protein p53/metabolism, Wnt Proteins/genetics, Wnt Proteins/metabolism, Biotechnology, Human, Signal Transduction, signaling pathway, EXPRESSION, Biochemistry & Molecular Biology, GENES, Pan-cancer, Therapeutics, General Biochemistry, Genetics and Molecular Biology, NO, Databases, 03 medical and health sciences, Genetic, Genetics, Combination therapy, Protein kinase B, Gene, SIGNATURES, Cancer genome atlas, Science & Technology, LANDSCAPE, MUTATIONS, Biochemistry, Genetics and Molecular Biology(all), Human Genome, Whole exome sequencing, Cell Biology, Transforming growth factor beta, cancer genome atla, 06 Biological Sciences, COMPREHENSIVE MOLECULAR CHARACTERIZATION, Wnt Proteins, therapeutic, Good Health and Well Being, 030104 developmental biology, Genes, PanCanAtla, biology.protein, Cancer research, Neoplasm, Phosphatidylinositol 3-Kinase, Tumor Suppressor Protein p53, Digestive Diseases, Genetics and Molecular Biology(all), Developmental Biology
Abstract

Genetic alterations in signaling pathways that control cell-cycle progression, apoptosis, and cell growth are common hallmarks of cancer, but the extent, mechanisms, and co-occurrence of alterations in these pathways differ between individual tumors and tumor types. Using mutations, copy-number changes, mRNA expression, gene fusions and DNA methylation in 9,125 tumors profiled by The Cancer Genome Atlas (TCGA), we analyzed the mechanisms and patterns of somatic alterations in ten canonical pathways: cell cycle, Hippo, Myc, Notch, Nrf2, PI-3-Kinase/Akt, RTK-RAS, TGFβ signaling, p53 and β-catenin/Wnt. We charted the detailed landscape of pathway alterations in 33 cancer types, stratified into 64 subtypes, and identified patterns of co-occurrence and mutual exclusivity. Eighty-nine percent of tumors had at least one driver alteration in these pathways, and 57% percent of tumors had at least one alteration potentially targetable by currently available drugs. Thirty percent of tumors had multiple targetable alterations, indicating opportunities for combination therapy. An integrated analysis of genetic alterations in 10 signaling pathways in >9,000 tumors profiled by TCGA highlights significant representation of individual and co-occurring actionable alterations in these pathways, suggesting opportunities for targeted and combination therapies. Michael Seiler, Peter G. Smith, Ping Zhu, Silvia Buonamici, and Lihua Yu are employees of H3 Biomedicine, Inc. Parts of this work are the subject of a patent application: WO2017040526 titled “Splice variants associated with neomorphic sf3b1 mutants.” Shouyoung Peng, Anant A. Agrawal, James Palacino, and Teng Teng are employees of H3 Biomedicine, Inc. Andrew D. Cherniack, Ashton C. Berger, and Galen F. Gao receive research support from Bayer Pharmaceuticals. Gordon B. Mills serves on the External Scientific Review Board of Astrazeneca. Anil Sood is on the Scientific Advisory Board for Kiyatec and is a shareholder in BioPath. Jonathan S. Serody receives funding from Merck, Inc. Kyle R. Covington is an employee of Castle Biosciences, Inc. Preethi H. Gunaratne is founder, CSO, and shareholder of NextmiRNA Therapeutics. Christina Yau is a part-time employee/consultant at NantOmics. Franz X. Schaub is an employee and shareholder of SEngine Precision Medicine, Inc. Carla Grandori is an employee, founder, and shareholder of SEngine Precision Medicine, Inc. Robert N. Eisenman is a member of the Scientific Advisory Boards and shareholder of Shenogen Pharma and Kronos Bio. Daniel J. Weisenberger is a consultant for Zymo Research Corporation. Joshua M. Stuart is the founder of Five3 Genomics and shareholder of NantOmics. Marc T. Goodman receives research support from Merck, Inc. Andrew J. Gentles is a consultant for Cibermed. Charles M. Perou is an equity stock holder, consultant, and Board of Directors member of BioClassifier and GeneCentric Diagnostics and is also listed as an inventor on patent applications on the Breast PAM50 and Lung Cancer Subtyping assays. Matthew Meyerson receives research support from Bayer Pharmaceuticals; is an equity holder in, consultant for, and Scientific Advisory Board chair for OrigiMed; and is an inventor of a patent for EGFR mutation diagnosis in lung cancer, licensed to LabCorp. Eduard Porta-Pardo is an inventor of a patent for domainXplorer. Han Liang is a shareholder and scientific advisor of Precision Scientific and Eagle Nebula. Da Yang is an inventor on a pending patent application describing the use of antisense oligonucleotides against specific lncRNA sequence as diagnostic and therapeutic tools. Yonghong Xiao was an employee and shareholder of TESARO, Inc. Bin Feng is an employee and shareholder of TESARO, Inc. Carter Van Waes received research funding for the study of IAP inhibitor ASTX660 through a Cooperative Agreement between NIDCD, NIH, and Astex Pharmaceuticals. Raunaq Malhotra is an employee and shareholder of Seven Bridges, Inc. Peter W. Laird serves on the Scientific Advisory Board for AnchorDx. Joel Tepper is a consultant at EMD Serono. Kenneth Wang serves on the Advisory Board for Boston Scientific, Microtech, and Olympus. Andrea Califano is a founder, shareholder, and advisory board member of DarwinHealth, Inc. and a shareholder and advisory board member of Tempus, Inc. Toni K. Choueiri serves as needed on advisory boards for Bristol-Myers Squibb, Merck, and Roche. Lawrence Kwong receives research support from Array BioPharma. Sharon E. Plon is a member of the Scientific Advisory Board for Baylor Genetics Laboratory. Beth Y. Karlan serves on the Advisory Board of Invitae.

Published
2018

13. Changes in Energy Metabolism in Pheochromocytoma

Author

Petrák, O., Haluzíková, D., Kaválková, P., Štrauch, B., Rosa, J., Holaj, R., Brabcová Vránková, A., Michalský, D., Haluzík, M., Zelinka, T., and Widimský, J., Jr

Published
2013

15. Erratum: The Immune Landscape of Cancer (Immunity (2018) 48(4) (812–830.e14), (S1074761318301213), (10.1016/j.immuni.2018.03.023))

Author

Thorsson, V., Gibbs, D. L., Brown, S. D., Wolf, D., Bortone, D. S., Ou Yang, T. -H., Porta-Pardo, E., Gao, G. F., Plaisier, C. L., Eddy, J. A., Ziv, E., Culhane, A. C., Paull, E. O., Sivakumar, I. K. A., Gentles, A. J., Malhotra, R., Farshidfar, F., Colaprico, A., Parker, J. S., Mose, L. E., N. S., Vo, Liu, J., Liu, Y., Rader, J., Dhankani, V., Reynolds, S. M., Bowlby, R., Califano, A., Cherniack, A. D., Anastassiou, D., Bedognetti, D., Mokrab, Y., Newman, A. M., Rao, A., Chen, K., Krasnitz, A., Hu, H., Malta, T. M., Noushmehr, H., Pedamallu, C. S., Bullman, S., Ojesina, A. I., Lamb, A., Zhou, W., Shen, H., Choueiri, T. K., Weinstein, J. N., Guinney, J., Saltz, J., Holt, R. A., Rabkin, C. S., Caesar-Johnson, S. J., Demchok, J. A., Felau, I., Kasapi, M., Ferguson, M. L., Hutter, C. M., Sofia, H. J., Tarnuzzer, R., Wang, Z., Yang, L., Zenklusen, J. C., Zhang, J. J., Chudamani, S., Lolla, L., Naresh, R., Pihl, T., Sun, Q., Wan, Y., Wu, Y., Cho, J., Defreitas, T., Frazer, S., Gehlenborg, N., Getz, G., Heiman, D. I., Kim, J., Lawrence, M. S., Lin, P., Meier, S., Noble, M. S., Saksena, G., Voet, D., Zhang, H., Bernard, B., Chambwe, N., Knijnenburg, T., Kramer, R., Leinonen, K., Miller, M., Reynolds, S., Shmulevich, I., Zhang, W., Akbani, R., Broom, B. M., Hegde, A. M., Ju, Z., Kanchi, R. S., Korkut, A., Li, J., Liang, H., Ling, S., Liu, W., Lu, Y., Mills, G. B., K. -S., Ng, Ryan, M., Wang, J., Zhang, J., Abeshouse, A., Armenia, J., Chakravarty, D., Chatila, W. K., de Bruijn, I., Gao, J., Gross, B. E., Heins, Z. J., Kundra, R., La, K., Ladanyi, M., Luna, A., Nissan, M. G., Ochoa, A., Phillips, S. M., Reznik, E., Sanchez-Vega, F., Sander, C., Schultz, N., Sheridan, R., Sumer, S. O., Sun, Y., Taylor, B. S., Anur, P., Peto, M., Spellman, P., Benz, C., Stuart, J. M., Wong, C. K., Yau, C., Hayes, D. N., Wilkerson, M. D., Ally, A., Balasundaram, M., Brooks, D., Carlsen, R., Chuah, E., Dhalla, N., Holt, R., Jones, S. J. M., Kasaian, K., Lee, D., Ma, Y., Marra, M. A., Mayo, M., Moore, R. A., Mungall, A. J., Mungall, K., Robertson, A. G., Sadeghi, S., Schein, J. E., Sipahimalani, P., Tam, A., Thiessen, N., Tse, K., Wong, T., Berger, A. C., Beroukhim, R., Cibulskis, C., Gabriel, S. B., Ha, G., Meyerson, M., Schumacher, S. E., Shih, J., Kucherlapati, M. H., Kucherlapati, R. S., Baylin, S., Cope, L., Danilova, L., Bootwalla, M. S., Lai, P. H., Maglinte, D. T., Van Den Berg, D. J., Weisenberger, D. J., Auman, J. T., Balu, S., Bodenheimer, T., Fan, C., Hoadley, K. A., Hoyle, A. P., Jefferys, S. R., Jones, C. D., Meng, S., Mieczkowski, P. A., Perou, A. H., Perou, C. M., Roach, J., Shi, Y., Simons, J. V., Skelly, T., Soloway, M. G., Tan, D., Veluvolu, U., Fan, H., Hinoue, T., Laird, P. W., Bellair, M., Chang, K., Covington, K., Creighton, C. J., Dinh, H., Doddapaneni, H., Donehower, L. A., Drummond, J., Gibbs, R. A., Glenn, R., Hale, W., Han, Y., Hu, J., Korchina, V., Lee, S., Lewis, L., Li, W., Liu, X., Morgan, M., Morton, D., Muzny, D., Santibanez, J., Sheth, M., Shinbrot, E., Wang, L., Wang, M., Wheeler, D. A., Xi, L., Zhao, F., Hess, J., Appelbaum, E. L., Bailey, M., Cordes, M. G., Ding, L., Fronick, C. C., Fulton, L. A., Fulton, R. S., Kandoth, C., Mardis, E. R., Mclellan, M. D., Miller, C. A., Schmidt, H. K., Wilson, R. K., Crain, D., Curley, E., Gardner, J., Lau, K., Mallery, D., Morris, S., Paulauskis, J., Penny, R., Shelton, C., Shelton, T., Sherman, M., Thompson, E., Yena, P., Bowen, J., Gastier-Foster, J. M., Gerken, M., Leraas, K. M., Lichtenberg, T. M., Ramirez, N. C., Wise, L., Zmuda, E., Corcoran, N., Costello, T., Hovens, C., Carvalho, A. L., de Carvalho, A. C., Fregnani, J. H., Longatto-Filho, A., Reis, R. M., Scapulatempo-Neto, C., Silveira, H. C. S., Vidal, D. O., Burnette, A., Eschbacher, J., Hermes, B., Noss, A., Singh, R., Anderson, M. L., Castro, P. D., Ittmann, M., Huntsman, D., Kohl, B., Le, X., Thorp, R., Andry, C., Duffy, E. R., Lyadov, V., Paklina, O., Setdikova, G., Shabunin, A., Tavobilov, M., Mcpherson, C., Warnick, R., Berkowitz, R., Cramer, D., Feltmate, C., Horowitz, N., Kibel, A., Muto, M., Raut, C. P., Malykh, A., Barnholtz-Sloan, J. S., Barrett, W., Devine, K., Fulop, J., Ostrom, Q. T., Shimmel, K., Wolinsky, Y., Sloan, A. E., De Rose, A., Giuliante, F., Goodman, M., Karlan, B. Y., Hagedorn, C. H., Eckman, J., Harr, J., Myers, J., Tucker, K., Zach, L. A., Deyarmin, B., Kvecher, L., Larson, C., Mural, R. J., Somiari, S., Vicha, A., Zelinka, T., Bennett, J., Iacocca, M., Rabeno, B., Swanson, P., Latour, M., Lacombe, L., Tetu, B., Bergeron, A., Mcgraw, M., Staugaitis, S. M., Chabot, J., Hibshoosh, H., Sepulveda, A., Su, T., Wang, T., Potapova, O., Voronina, O., Desjardins, L., Mariani, O., Roman-Roman, S., Sastre, X., Stern, M. -H., Cheng, F., Signoretti, S., Berchuck, A., Bigner, D., Lipp, E., Marks, J., Mccall, S., Mclendon, R., Secord, A., Sharp, A., Behera, M., Brat, D. J., Chen, A., Delman, K., Force, S., Khuri, F., Magliocca, K., Maithel, S., Olson, J. J., Owonikoko, T., Pickens, A., Ramalingam, S., Shin, D. M., Sica, G., Van Meir, E. G., Eijckenboom, W., Gillis, A., Korpershoek, E., Looijenga, L., Oosterhuis, W., Stoop, H., van Kessel, K. E., Zwarthoff, E. C., Calatozzolo, C., Cuppini, L., Cuzzubbo, S., Dimeco, F., Finocchiaro, G., Mattei, L., Perin, A., Pollo, B., Chen, C., Houck, J., Lohavanichbutr, P., Hartmann, A., Stoehr, C., Stoehr, R., Taubert, H., Wach, S., Wullich, B., Kycler, W., Murawa, D., Wiznerowicz, M., Chung, K., Edenfield, W. J., Martin, J., Baudin, E., Bubley, G., Bueno, R., De Rienzo, A., Richards, W. G., Kalkanis, S., Mikkelsen, T., Scarpace, L., Girard, N., Aymerich, M., Campo, E., Gine, E., Guillermo, A. L., Van Bang, N., Hanh, P. T., Phu, B. D., Tang, Y., Colman, H., Evason, K., Dottino, P. R., Martignetti, J. A., Gabra, H., Juhl, H., Akeredolu, T., Stepa, S., Hoon, D., Ahn, K., Kang, K. J., Beuschlein, F., Breggia, A., Birrer, M., Bell, D., Borad, M., Bryce, A. H., Castle, E., Chandan, V., Cheville, J., Copland, J. A., Farnell, M., Flotte, T., Giama, N., Ho, T., Kendrick, M., Kocher, J. -P., Kopp, K., Moser, C., Nagorney, D., O'Brien, D., O'Neill, B. P., Patel, T., Petersen, G., Que, F., Rivera, M., Roberts, L., Smallridge, R., Smyrk, T., Stanton, M., Thompson, R. H., Torbenson, M., Yang, J. D., Zhang, L., Brimo, F., Ajani, J. A., Gonzalez, A. M. A., Behrens, C., Bondaruk, J., Broaddus, R., Czerniak, B., Esmaeli, B., Fujimoto, J., Gershenwald, J., Guo, C., Lazar, A. J., Logothetis, C., Meric-Bernstam, F., Moran, C., Ramondetta, L., Rice, D., Sood, A., Tamboli, P., Thompson, T., Troncoso, P., Tsao, A., Wistuba, I., Carter, C., Haydu, L., Hersey, P., Jakrot, V., Kakavand, H., Kefford, R., Lee, K., Long, G., Mann, G., Quinn, M., Saw, R., Scolyer, R., Shannon, K., Spillane, A., Stretch, O., Synott, M., Thompson, J., Wilmott, J., Al-Ahmadie, H., Chan, T. A., Ghossein, R., Gopalan, A., Levine, D. A., Reuter, V., Singer, S., Singh, B., Tien, N. V., Broudy, T., Mirsaidi, C., Nair, P., Drwiega, P., Miller, J., Smith, J., Zaren, H., Park, J. -W., Hung, N. P., Kebebew, E., Linehan, W. M., Metwalli, A. R., Pacak, K., Pinto, P. A., Schiffman, M., Schmidt, L. S., Vocke, C. D., Wentzensen, N., Worrell, R., Yang, H., Moncrieff, M., Goparaju, C., Melamed, J., Pass, H., Botnariuc, N., Caraman, I., Cernat, M., Chemencedji, I., Clipca, A., Doruc, S., Gorincioi, G., Mura, S., Pirtac, M., Stancul, I., Tcaciuc, D., Albert, M., Alexopoulou, I., Arnaout, A., Bartlett, J., Engel, J., Gilbert, S., Parfitt, J., Sekhon, H., Thomas, G., Rassl, D. M., Rintoul, R. C., Bifulco, C., Tamakawa, R., Urba, W., Hayward, N., Timmers, H., Antenucci, A., Facciolo, F., Grazi, G., Marino, M., Merola, R., de Krijger, R., Gimenez-Roqueplo, A. -P., Piche, A., Chevalier, S., Mckercher, G., Birsoy, K., Barnett, G., Brewer, C., Farver, C., Naska, T., Pennell, N. A., Raymond, D., Schilero, C., Smolenski, K., Williams, F., Morrison, C., Borgia, J. A., Liptay, M. J., Pool, M., Seder, C. W., Junker, K., Omberg, L., Dinkin, M., Manikhas, G., Alvaro, D., Bragazzi, M. C., Cardinale, V., Carpino, G., Gaudio, E., Chesla, D., Cottingham, S., Dubina, M., Moiseenko, F., Dhanasekaran, R., Becker, K. -F., Janssen, K. -P., Slotta-Huspenina, J., Abdel-Rahman, M. H., Aziz, D., Bell, S., Cebulla, C. M., Davis, A., Duell, R., Elder, J. B., Hilty, J., Kumar, B., Lang, J., Lehman, N. L., Mandt, R., Nguyen, P., Pilarski, R., Rai, K., Schoenfield, L., Senecal, K., Wakely, P., Hansen, P., Lechan, R., Powers, J., Tischler, A., Grizzle, W. E., Sexton, K. C., Kastl, A., Henderson, J., Porten, S., Waldmann, J., Fassnacht, M., Asa, S. L., Schadendorf, D., Couce, M., Graefen, M., Huland, H., Sauter, G., Schlomm, T., Simon, R., Tennstedt, P., Olabode, O., Nelson, M., Bathe, O., Carroll, P. R., Chan, J. M., Disaia, P., Glenn, P., Kelley, R. K., Landen, C. N., Phillips, J., Prados, M., Simko, J., Smith-McCune, K., Vandenberg, S., Roggin, K., Fehrenbach, A., Kendler, A., Sifri, S., Steele, R., Jimeno, A., Carey, F., Forgie, I., Mannelli, M., Carney, M., Hernandez, B., Campos, B., Herold-Mende, C., Jungk, C., Unterberg, A., von Deimling, A., Bossler, A., Galbraith, J., Jacobus, L., Knudson, M., Knutson, T., Ma, D., Milhem, M., Sigmund, R., Godwin, A. K., Madan, R., Rosenthal, H. G., Adebamowo, C., Adebamowo, S. N., Boussioutas, A., Beer, D., Giordano, T., Mes-Masson, A. -M., Saad, F., Bocklage, T., Landrum, L., Mannel, R., Moore, K., Moxley, K., Postier, R., Walker, J., Zuna, R., Feldman, M., Valdivieso, F., Dhir, R., Luketich, J., Pinero, E. M. M., Quintero-Aguilo, M., Carlotti, C. G., Dos Santos, J. S., Kemp, R., Sankarankuty, A., Tirapelli, D., Catto, J., Agnew, K., Swisher, E., Creaney, J., Robinson, B., Shelley, C. S., Godwin, E. M., Kendall, S., Shipman, C., Bradford, C., Carey, T., Haddad, A., Moyer, J., Peterson, L., Prince, M., Rozek, L., Wolf, G., Bowman, R., Fong, K. M., Yang, I., Korst, R., Rathmell, W. K., Fantacone-Campbell, J. L., Hooke, J. A., Kovatich, A. J., Shriver, C. D., Dipersio, J., Drake, B., Govindan, R., Heath, S., Ley, T., Van Tine, B., Westervelt, P., Rubin, M. A., Lee, J. I., Aredes, N. D., Mariamidze, A., Serody, J. S., Demicco, E. G., Disis, M. L., and Vincent, B. G.

Subjects
immune, cancer, methods
Published
2019

18. Smart as a Key Component of the Sustainable City Development

Author

Zelinka, T., Ondrej Pribyl, and Lom, M.

Subjects
Smart city, Agile, Sustainability, lcsh:T58.5-58.64, lcsh:Information technology, Systems Engineering, SCRUM, lcsh:P87-96, lcsh:Communication. Mass media
Abstract

Smart City Initiatives are aiming on creation of a sustainable model for cities with the aim to improve quality of life of their citizens. A smart city represents an interdisciplinary field requiring high level of cooperation among experts from different fields and a contribution of the latest technologies in order to achieve the best results in the city's key areas. Such approach requires an effective cooperation across many fields, from technical or economic through legislation to social areas. Success of the smart city concept is not thinkable without an effective engagement of the end users, i.e. citizens of the smart cities. The traditional systems engineering methodologies fail and new approaches are urgently needed. A new Hybrid-Agile Methodology (HAM) is introduced and its advantages with respect to smart city projects are discussed. However, application of methodologies cannot be successful without principal changes in how are all engaged parties thinking.

Published
2016

20. Authentication and Data Security in ITS Telecommunications Solutions

Author

Zelinka, T., Jerabek, M., and Zdenek Lokaj

Subjects
Authentication, Performance Indicator, lcsh:T58.5-58.64, Intelligent Transport System, lcsh:Information technology, Object Identification, System Performance, Telematics, data security, lcsh:P87-96, lcsh:Communication. Mass media
Abstract

Paper presents telecommunications security issues with dynamically changing networking. Paper also presents performance indicators of authentication as an integral part of the approach to non-public information. Expected level of security depend on relevant ITS services requirements, different solutions require different levels of quality. Data volumes transferred both in private data vehicle on board networks as well as between vehicles and infrastructure or other vehicles significantly and progressively grow. This trend leads to increase of the fatal problems if security of the wide area networks is not relevantly treated. Relevant communications security treatment becomes crucial part of the ITS telecommunications solution because probability of hazards appearances grow if vehicles networks are integrated in the dynamically organized wide area networks. Besides of available "off shelf" security tools solution based on non-public universal identifier with dynamical extension and data selection according to actor role or category is presented including performances indicators for the authentication process.

Published
2014

21. Service Quality Management in the ITS Telecommunications Systems

Author

Zelinka, T., Zdenek Lokaj, and Stotyr, M.

Subjects
lcsh:T58.5-58.64, Intelligent Transport System, lcsh:Information technology, Telematics, system performance, moving object identification, data security, lcsh:P87-96, lcsh:Communication. Mass media
Abstract

Guaranteed selected quality of telecommunication service and wide area coverage are typical requirements of the ITS (Intelligent Transport Systems) applications. Extensive range of wireless data services with reasonable coverage is provided by public wireless services operators, however, mostly no guaranteed relevant range of quality and security is available. ITS services require cost-effectively solution which can be resolved by combination of the "core" public solution with the other public as well as private services where and when it is needed. Such approach requires implementation of the relevant flexible system architecture supported by the efficient decision processes. ITS specific service security requirements would not underestimated, as well. Special situation is identified in case of the C2I (Car to Infrastructure) and C2C (Car to Car) communication namely if the vehicle on board unit is interconnected with the vehicle CAN (Controlled Area Network) based network. Such configurations significantly increase potential of dangerous intruders´ attacks. Probability of the critical hazards appearances grows if the ITS data are accessible in the wide area networks. That is also the main reason why relevant telecommunications security support is understood as one of the crucial part of the ITS telecommunications solution.

Published
2013

24. A systematic review on the genetic analysis of paragangliomas: primarily focused on head and neck paragangliomas.

Author

GUHA, A., MUSIL, Z., VICHA, A., ZELINKA, T., PACAK, K., ASTL, J., and CHOVANEC, M.

Subjects
PARAGANGLIOMA, PHEOCHROMOCYTOMA, NEUROENDOCRINE tumors, HEAD & neck cancer, SOMATIC mutation
Abstract

Paragangliomas and pheochromocytomas are rare, mostly benign neuroendocrine tumors, which are embryologically derived from neural crest cells of the autonomic nervous system. Paragangliomas are essentially the extra-adrenal counterparts of pheochromocytomas. As such, this family of tumors can be subdivided into head and neck paragangliomas, pheochromocytomas, and thoracic and abdominal extra-adrenal paragangliomas. Ten out of fifteen genes that contribute to the development of paragangliomas are more susceptible to the development of head and neck paragangliomas when mutated. Gene expression profiling revealed that pheochromocytomas and paragangliomas could be classified into two main clusters (C1 and C2) based on transcriptomes. These groups were defined according to their mutational status and as such strongly associated with specific tumorigenic pathways. The influence of the main genetic drivers on the somatic molecular phenotype was shown by DNA methylation and miRNA profiling. Certain subunits of succinate dehydrogenase (SDHx), von Hippel-Lindau (VHL) and transmembrane protein 127 (TMEM127) still have the highest impact on development of head and neck paragangliomas. The link between RAS proteins and the formation of pheochromocytomas and paragangliomas is clear due to the effect of receptor tyrosine-protein kinase (RET) and neurofibromatosis type 1 (NF1) in RAS signaling and recent discovery of the role of HRAS. The functions of MYC-associated factor X (MAX) and prolyl hydroxylase 2 (PHD2) mutations in the contribution to the pathogenesis of paragangliomas still remain unclear. Ongoing studies give us an insight into the incidence of germline and somatic mutations, thus offering guidelines for early detection. Furthermore, these also show the risk of mistakenly assuming sporadic cases in the absence of definitive family history in head and neck paragangliomas. [ABSTRACT FROM AUTHOR]

Published
2019
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26. The Effect of Adrenalectomy on Exercise Response of the Renin-Angiotensin-Aldosterone System and Exercise Tolerance in Primary Aldosteronism.

Author

TUKA, V., MATOULEK, M., ROSA, J., PETRÁK, O., MIKEŠ, O., KRÁTKÁ, Z., ŠTRAUCH, B., HOLAJ, R., ZELINKA, T., and WIDIMSKÝ, J.

Subjects
ADRENALECTOMY, HYPERALDOSTERONISM, PHYSICAL fitness, RENIN-angiotensin system, CARDIOPULMONARY fitness, PATIENTS
Abstract

Primary aldosteronism (PA) is associated with objectively measured lower physical fitness and blunted response of the renin-angiotensin-aldosterone system to exercise. The purpose of this pilot study was to objectively measure exercise response of the renin-angiotensin-aldosterone system and cardiopulmonary fitness changes after laparoscopic adrenalectomy (ADE) in patients with unilateral PA. We examined a total of 14 patients with confirmed PA before and after ADE, by means of spiroergometry and hormonal evaluation. As expected, after adrenalectomy basal aldosterone (Aldo) levels before exercise decreased significantly, with a concomitant increase in plasma renin (PR). The increase in Aldo (285.9±171.3 to 434.1± 278.2 ng/l; p=0.02) and blunted increase in PR (7.1±0.4 to 8.9±10.4 pg/ml; NS) post-exercise before ADE became significant after ADE Aldo post-ADE (46.8±18.8 to 106.5± 68.1 ng/l; p<0.0001) and PR post-ADE (20.1±14.5 to 33.9± 30.7 pg/ml; p=0.014). After adrenalectomy, the patients had a non-significant increase in peak workload and VO2peak. We found normalization of the renin-angiotensin-aldosterone system response to exercise with little changes in cardiopulmonary fitness six months after ADE. [ABSTRACT FROM AUTHOR]

Published
2018
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29. Radioimmunoassay of Chromogranin A and Free Metanephrines in Diagnosis of Pheochromocytoma.

Author

BÍLEK, R., ZELINKA, T., VLČEK, P., DUŠKOVÁ, J., MICHALSKÝ, D., NOVÁK, K., VÁCLAVÍKOVÁ, E., and WIDIMSKÝ Jr., J.

Subjects
RADIOIMMUNOASSAY, CHROMOGRANINS, PHEOCHROMOCYTOMA, PARAGANGLIOMA, ADRENAL surgery, CHRONIC kidney failure, DIAGNOSIS
Abstract

This work discusses the clinical performance of chromogranin A, free metanephrine and normetanephrine determination in plasma using a radioimmunoanalytical methods for the diagnosis of pheochromocytoma and paraganglioma. Blood samples were collected from 55 patients (46 pheochromocytomas, 9 paragangliomas). A sampling of biological materials was performed preoperatively and about one week, six months and one year after adrenal gland surgery. The comparative group without a diagnosis of pheochromocytoma/paraganglioma consisted of 36 pheochromocytoma/paraganglioma patients more than 4 months after adrenal gland surgery, and of 87 patients, 16 of them with multiple endocrine neoplasia, 9 with medullary and 5 with parafolicullar carcinoma of the thyroid gland. The rest were patients with various adrenal gland disorders. Chromogranin A, metanephrine and normetanephrine were determined in the EDTA-plasma using a radioimmunoassay kits Cisbio Bioassays, France and IBL International GmbH, Germany. Clinical sensitivity was 96 % for the combination of metanephrine and normetanephrine, and 93 % for chromogranin A. Clinical specificity was 100 % for the combination metanephrine and normetanephrine, and 96 % for chromogranin A. Falsely elevated levels of chromogranin A were observed in 1 patient with chronic renal insufficiency and 9 analyses were influenced by the administration of proton pump inhibitors. These results were excluded of CGA specificity. Both the combination of plasma free metanephrine, normetanephrine and chromogranin A as determined by radioimmunoassays, which are simple without the necessity of special laboratory material, are effective markers of pheochromocytoma or paraganglioma. Chromogranin A exerts association to malignity and all markers are associated with tumor mass. [ABSTRACT FROM AUTHOR]

Published
2017
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30. Lower Physical Fitness in Patients With Primary Aldosteronism Is Linked to the Severity of Hypertension and Kalemia.

Author

TUKA, V., MATOULEK, M., ZELINKA, T., ROSA, J., PETRÁK, O., MIKEŠ, O., KRÁTKÁ, Z., ŠTRAUCH, B., HOLAJ, R., and WIDIMSKÝ Jr., J.

Subjects
HYPERALDOSTERONISM, HYPERTENSION, REGULATION of blood pressure, PHYSIOLOGICAL aspects of physical fitness, CARDIOPULMONARY fitness measurement
Abstract

Hypokalemia as a typical feature of primary aldosteronism (PA) is associated with muscle weakness and could contribute to lower cardiopulmonary fitness. The aim of this study was to describe cardiopulmonary fitness and exercise blood pressure and their determinants during a symptom-limited exercise stress test in patients with PA. We performed a cross-sectional study of patients with confirmed PA who were included before adrenal vein sampling on whom a symptom-limited exercise stress test with expired gas analysis was performed. Patients were switched to the treatment with doxazosin and verapamil at least two weeks before the study. In 27 patients (17 male) the VO2peak was 25.4±6.0 ml/kg/min which corresponds to 80.8±18.9 % of Czech national norm. Linear regression analysis shows that VO2peak depends on doxazosin dose (DX) (p=0.001) and kalemia (p=0.02): VO2peak = 4.2 - 1.0 * DX + 7.6 * Kalemia. Patients with higher doxazosin doses had a longer history of hypertension and had used more antihypertensives before examination, thus indicating that VO2peak also depends on the severity of hypertension. In patients with PA, lower cardiopulmonary fitness depends inversely on the severity of hypertension and on lower plasma potassium level. [ABSTRACT FROM AUTHOR]

Published
2017
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32. Inflammatory Markers in Primary Aldosteronism.

Author

ŠOMLÓOVÁ, Z., PETRÁK, O., ROSA, J., ŠTRAUCH, B., INDRA, T., ZELINKA, T., HALUZÍK, M., ZIKÁN, V., HOLAJ, R., and WIDIMSKÝ Jr., J.

Subjects
HYPERALDOSTERONISM, HYPERTENSION, INFLAMMATION, CYTOKINES, ALDOSTERONE
Abstract

Primary aldosteronism (PA) is the most common cause of endocrine hypertension with a high frequency of cardiovascular complications. The unfavorable cardiometabolic profile may be due to aldosterone-mediated activation of inflammatory cells, circulatory cytokines and activation of collagen synthesis in the vessel wall. Aim of our study was to evaluate differences in the levels of hsCRP, IL-6, TNF-α and N-terminal propeptide of collagen I (PINP) in patients with PA and essential hypertension (EH) as a control group, and between the subtypes of PA (aldosterone producing adenoma - APA, idiopathic hyperaldosteronism - IHA). We studied 28 patients with PA (IHA - 10 patients, APA - 12 patients, 6 unclassified) and 28 matched patients with EH. There were no differences in the levels of inflammatory markers between the followed groups [EH vs. PA: TNF-α (5.09 [3.68-6.32] vs. 4.84 [3.62-6.50] pg/ml), IL-6 (0.94 [0.70-1.13] vs. 0.97 [0.71-1.28] pg/ml), hsCRP (0.53 [0.25-1.54] vs. 0.37 [0.31-0.61] mg/l), leukocytes (6.35±1.42 vs. 5.97±1.29 109 l); APA vs. IHA: TNF-α (4.54 [3.62-7.03] vs. 5.19 [4.23-5.27] pg/ml), IL-6 (0.96 [0.63-1.21] vs. 0.90 [0.65-1.06] pg/ml), hsCRP (0.34 [0.29-0.47] vs. 0.75 [0.36-1.11] mg/l), leukocytes (6.37±1.41 vs. 5.71±1.21 109 l)]. Significant differences in the levels of PINP between PA and EH group were observed (35.18 [28.46-41.16] vs. 45.21 [36.95-62.81] μg/l, p≤0.003). No differences in inflammatory markers were observed between the followed groups, we confirmed higher levels of PINP in patients with PA. [ABSTRACT FROM AUTHOR]

Published
2016

33. Biochemical Testing After Pheochromocytoma Removal: How Early?

Author

Zelinka, T., Petrák, O., Hamplová, B., Turková, H., Waldauf, P., Rosa, J., Šomlóová, Z., Holaj, R., Štrauch, B., Indra, T., Kršek, M., Brabcová Vránková, A., Musil, Z., Dušková, J., Kubinyi, J., Michalský, D., Novák, K., and Widimský Jr., J.

Subjects
*PHEOCHROMOCYTOMA, *TUMOR treatment, *POSTOPERATIVE care, *BIOCHEMISTRY, *BLOOD plasma, *THERAPEUTICS
Abstract

Pheochromocytomas are catecholamine-producing tumors with typical clinical presentation. Tumor resection is considered as an appropriate treatment strategy. Due to its unpredictable clinical behavior, biochemical testing is mandatory to confirm the success of tumor removal after surgery. The aim of the study was to investigate the feasibility of a shorter interval of postoperative testing (earlier than the recommended 2-4 weeks according to recently published Guidelines). We investigated 81 patients with pheochromocytoma before and after surgery. Postoperative examination was performed of stable subjects after their transport from the surgical to the internal ward (7.1 ± 2.2 days after surgery). Plasma metanephrines were used for the diagnosis of pheochromocytoma and confirmation of successful tumor removal. All subjects with pheochromocytoma had markedly elevated plasma metanephrines before surgery. No correlation between postoperative interval (the shortest being 3 days) and plasma metanephrine levels was found. Postoperative plasma metanephrine levels did not differ significantly from those taken at the one-year follow-up. In conclusion, we have shown that early postoperative diagnostic workup of subjects with pheochromocytoma is possible and may thus simplify early postoperative management of this clinical condition. [ABSTRACT FROM AUTHOR]

Published
2015
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34. Deconjugated Urinary Metanephrine, Normetanephrine and 3-Methoxytyramine in Laboratory Diagnosis of Pheochromocytoma and Paraganglioma.

Author

BÍLEK, R., ZELINKA, T., VLČEK, P., DUŠKOVÁ, J., MICHALSKÝ, D., NOVÁK, K., BEŠŤÁK, J., and WIDIMSKÝ Jr., J.

Subjects
PHEOCHROMOCYTOMA, PARAGANGLIOMA, ADRENAL surgery, CHROMATOGRAPHIC analysis, PERFORMANCE evaluation, DIAGNOSIS
Abstract

This work discusses the clinical performance of deconjugated metanephrine (MN), normetanephrine (NMN) and 3-methoxytyramine (3MT) determined in the basal first morning urine using a chromatographic method with electrochemical detection for the clinical diagnosis of pheochromocytoma (PHEO) and paraganglioma (PGL). Urine samples were collected from 44 patients (36 with PHEO, 8 with PGL) aged 54+/-17 (20-78) years (22 females, 22 males). A sampling of biological materials was performed preoperatively and about one week, six months and one year after adrenal gland surgery. The control group consisted of 34 PHEO/PGL patients more than 4 months after adrenal gland surgery. All subjects in the control group were without a diagnosis of PHEO or PGL. Clinical sensitivity was 55% for MN, 64% for NMN, 80% for combination of both MN and NMN, and only 23% for 3TM. Clinical specificity calculated from the control group was 93% for MN, 95% for NMN, 95% for the combination MN and NMN, and 97% for 3TM. Cut-off values for deconjugated metanephrines in the basal urine were 310 (MN), 690 (NMN) and 250 µg/l (3MT). Chromatographic determination of deconjugated urinary metanephrines, which is simple without the necessity of special laboratory material, can serve for the screening of PHEO or PGL patients. Urine NMN and 3MT exerts an association to malignity, and all markers are associated with tumor mass. However, the principal laboratory diagnosis of PHEO or PGL must be based on plasma-free metanephrines and plasma chromogranin A with better performance in the laboratory diagnosis of PHEO or PGL. [ABSTRACT FROM AUTHOR]

Published
2015
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37. Three Months of Regular Aerobic Exercise in Patients With Obesity Improve Systemic Subclinical Inflammation Without Major Influence on Blood Pressure and Endocrine Production of Subcutaneous Fat.

Author

TRACHTA, P., DRÁPALOVÁ, J., KAVÁLKOVÁ, P., TOUŠKOVÁ, V., CINKAJZLOVÁ, A., LACINOVÁ, Z., MATOULEK, M., ZELINKA, T., WIDIMSKÝ Jr., J., MRÁZ, M., and HALUZÍK, M.

Subjects
AEROBIC exercises, INFLAMMATION, BLOOD pressure, ANTHROPOMETRY, BIOCHEMISTRY, ADIPOSE tissues
Abstract

The aim of our study was to explore the effects of regular aerobic exercise on anthropometric, biochemical and hormonal parameters and mRNA expression of selected factors involved in metabolic regulations in subcutaneous adipose tissue of patients with obesity. Fifteen obese women with arterial hypertension underwent a three-month exercise program consisting of 30 min of aerobic exercise 3 times a week. Fifteen healthy lean women with no intervention served as a control group. Obese group underwent anthropometric measurements, blood sampling, subcutaneous adipose tissue (SCAT) biopsy and 24-h blood pressure monitoring at baseline and after three months of exercise, while control group was examined only once. At baseline, obese group had increased SCAT expression of proinflammatory cytokines and adipokines relative to control group. Three months of regular exercise improved anthropometric parameters, decreased CRP, blood glucose and HOMA-IR, while having no significant effect on lipid profile and blood pressure. Gene expressions in SCAT were not affected by physical activity with the exception of increased aquaporin-3 mRNA expression. We conclude that three months of regular exercise decrease systemic subclinical inflammation with only minor influence on the blood pressure and the endocrine function of subcutaneous fat. [ABSTRACT FROM AUTHOR]

Published
2014
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38. HIF Signaling Pathway in Pheochromocytoma and Other Neuroendocrine Tumors.

Author

JOCHMANOVÁ, I., ZELINKA, T., WIDIMSKÝ Jr., J., and PACAK, K.

Subjects
HYPOXIA-inducible factors, PHEOCHROMOCYTOMA, NEUROENDOCRINE tumors, TRANSCRIPTION factors, IRON metabolism, ERYTHROPOIESIS, NEOPLASTIC cell transformation
Abstract

Hypoxia-inducible factors (HIFs) are transcription factors controlling energy, iron metabolism, erythropoiesis, and development. Dysregulation of these proteins contributes to tumorigenesis and cancer progression. Recent findings revealed the important role of HIFs in the pathogenesis of neuroendocrine tumors, especially pheochromocytoma (PHEO) and paraganglioma (PGL). PHEOs and PGLs are catecholamineproducing tumors arising from sympathetic- or parasympatheticderived chromaffin tissue. To date, eighteen PHEO/PGL susceptibility genes have been identified. Based on the main signaling pathways, PHEOs/PGLs have been divided into two clusters, pseudohypoxic cluster 1 and cluster 2, rich in kinase receptor signaling and protein translation pathways. Recent data suggest that both clusters are interconnected via the HIF signaling and its role in tumorigenesis is supported by newly described somatic and germline mutations in HIF2A gene in patients with PHEOs/PGLs associated with polycythemia, and in some of them also with somatostatinoma. Moreover, HIFa signaling has also been shown to be upregulated in neuroendocrine tumors other than PHEO/PGL. Some of these tumors are components of hereditary tumor syndromes which can be associated with PHEO/PGL, but also in ileal carcinoids or melanoma. HIF signaling appears to be one of the crucial players in tumorigenesis, which could suggest new therapeutic approaches for treatment of neuroendocrine tumors. [ABSTRACT FROM AUTHOR]

Published
2014
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40. Peripheral Arterial Stiffness in Primary Aldosteronism.

Author

ROSA, J., ŠOMLÓOVÁ, Z., PETRÁK, O., ŠTRAUCH, B., INDRA, T., ŠENITKO, M., ZELINKA, T., HOLAJ, R., and WIDIMSKÝ Jr, J.

Subjects
ARTERIAL diseases, HYPERALDOSTERONISM, ALDOSTERONE, COLLAGEN, GROWTH factors, HYPERTENSION, BLOOD pressure
Abstract

Aldosterone overproduction increases arterial wall stiffness by accumulation of different types of collagen fibres and growth factors. Our previous studies showed that central (aortic) arterial stiffness is increased in primary aldosteronism (PA) independently of concomitant hypertension and that these changes might be reversible after successful adrenalectomy. There is limited data available on the potential impact of mineralocorticoid overproduction on the deterioration of peripheral arterial stiffness. The current study was thus aimed at investigating the effect of aldosterone overproduction on peripheral arterial stiffness assessed by peripheral (femoralankle) pulse wave velocity (PWV) in PA patients compared with essential hypertension (EH) patients. Forty-nine patients with confirmed PA and 49 patients with EH were matched for age, blood pressure, body mass index, lipid profile, and fasting glucose. PWV was obtained using the Sphygmocor applanation tonometer. Both peripheral and central PWV were significantly higher in PA patients compared to EH patients, while clinical blood pressures were similar. Plasma aldosterone level was the main predictor of peripheral PWV in PA. Our data indicate aldosterone overproduction in PA does not preferentially affect central arterial system. Fibroproliferative effect of higher aldosterone levels lead to alteration of central-elastic as well as peripheral-muscular arteries with subsequent increase in its stiffness. [ABSTRACT FROM AUTHOR]

Published
2012
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41. Have Main Types of Primary Aldosteronism Different Phenotype?

Author

Šomlóová, Z., Indra, T., Rosa, J., Petrák, O., Štrauch, B., Zelinka, T., Holaj, R., and Widimský Jr., J.

Subjects
HYPERALDOSTERONISM, PHENOTYPES, HYPERTENSION, ENDOCRINE diseases, CARDIOVASCULAR diseases, DISEASE complications, MEDICAL statistics
Abstract

Primary aldosteronism (PA) is the most common cause of endocrine hypertension with a high frequency of cardiovascular complications. We found in our previous study higher occurrence of metabolic disturbances in patients with idiopathic hyperaldosteronism (IHA) compared to subjects with aldosterone-producing adenoma (APA). The aim of our present study is to evaluate potential differences in the frequency of endorgan damage (arterial stiffness and microalbuminuria) between two main types of PA. The diagnosis of the particular form of PA was based on adrenal venous sampling and/or histopathological examination. We analyzed clinical and laboratory data from 72 patients with PA (36 with IHA, 36 with APA). The arterial stiffness was expressed as the carotid-femoral pulse wave velocity (PWV) and the renal damage as urinary albumin excretion levels (UAE). Patients with IHA had significantly (p<0.03) higher prevalence of metabolic syndrome (17 % in APA, 35 % in IHA), higher triglycerides (1.37±0.71 mmol/l in APA, 1.85±0.87 mmol/l in IHA), lower HDL cholesterol (1.25±0.28 mmol/l in APA, 1.06±0.25 mmol/l in IHA), higher PWV (7.91±1.61 m/s in APA, 8.99±1.77 m/s in IHA) and higher UAE (12.93±2.21 mg/l in APA, 28.09±6.66 mg/l in IHA). It seems that patients with IHA may have a slightly different phenotype compared to APA. [ABSTRACT FROM AUTHOR]

Published
2012
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42. Vascular Disturbances in Primary Aldosteronism: Clinical Evidence.

Author

Widimsky Jr., J., Strauch, B., Petrák, O., Rosa, J., Somloova, Z., Zelinka, T., and Holaj, R.

Subjects
HYPERALDOSTERONISM, HYPERTENSION, OXIDATIVE stress, BLOOD-vessel abnormalities, VASCULAR remodeling, ARTERIAL diseases
Abstract

Primary aldosteronism (PA) is a common form of arterial hypertension with a high prevalence of cardiovascular complications. In patients with PA, complex mechanisms may lead to functional and/or structural abnormalities of the blood vessel wall. Clinical evidence indicates that patients with PA may have immune cell activation, increased oxidative stress, impaired endothelial function and vascular remodeling. Activation of fibroproliferation has been found in resistant arteries of patients with PA. Subjects with PA compared to essential hypertensives with similar blood pressure levels have increased intima-media thickness and arterial stiffness as measured by pulse wave velocity. These functional and morphological changes can be m odified by an increased sodium intake. Vascular remodeling in PA may indicate a poor response to specific therapy with lower probability of cure and/or normalization of blood pressure. Early diagnosis of PA before blood vessel wall disturbances develop is of utmost importance. [ABSTRACT FROM AUTHOR]

Published
2012
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43. The Effect of Pheochromocvtoma Treatment on Subclinical Inflammation and Endocrine Function of Adipose Tissue.

Author

BOŠANSKÁ, L., PETRÁK, O., ZELINKA, T., MRÁZ, M., WIDIMSKÝ, Jr., J., and HALUZÍK, M.

Subjects
INFLAMMATION, ADIPOSE tissues, C-reactive protein, BLOOD sugar, SERUM, LEPTIN
Abstract

The aim of our study was to evaluate the influence of surgical removal of pheochromocytoma on the endocrine function of adipose tissue and subclinical inflammation as measured by circulating C-reactive protein (CRP) levels. Eighteen patients with newly diagnosed pheochromocytoma were included into study. Anthropometric measures, biochemical parameters, serum CRP, leptin, adiponectin and resistin levels were measured at the time of diagnosis and six months after surgical removal of pheochromocytoma. Surgical removal of pheochromocytoma significantly increased body weight, decreased both systolic and diastolic blood pressure, fasting blood glucose and glycated hemoglobin levels. Serum CRP levels were decreased by 50 % six months after surgical removal of pheochromocytoma (0.49±0.12 vs. 0.23±0.05 mg/l, p<0.05) despite a significant increase in body weight. Serum leptin, adiponectin and resistin levels were not affected by the surgery. We conclude that increased body weight in patients after surgical removal of pheochromocytoma is accompanied by an attenuation of subclinical inflammation probably due to catecholamine normalization. We failed to demonstrate an involvement of the changes in circulating leptin, adiponectin or resistin levels in this process. [ABSTRACT FROM AUTHOR]

Published
2009
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44. Relationship Between Clinical, 24-Hour, Average Day-Time and Night-Time Blood Pressure and Measures of Arterial Stiffness in Essential Hypertension.

Author

Rosa, J., Štrauch, B., Petrák, O., Pikus, T., Holaj, R., Zelinka, T., Wichterle, D., and Widimský Jr., J.

Subjects
BLOOD pressure measurement, ARTERIAL diseases, HYPERTENSION, CARDIOVASCULAR diseases risk factors, MULTIPLE regression analysis, PHYSIOLOGICAL research
Abstract

Arterial wall stiffness is considered an independent cardiovascular risk factor. Aim of this study was to evaluate relationship between clinical, 24-hour, average day-time and night-time blood pressure (BP) and measures of arterial stiffness assessed by pulse wave velocity (PWV) (using SphygmoCor applanation tonometer) in essential hypertension (severe-resistant (RH, n=29) and moderate hypertension (EH, n=35)) and in normotensive control subjects (n-29) (NCS) matched by age. After multiple regression analysis, PWV remains significantly correlated mainly with night-time pulse pressure and to a lesser extent with age. PWV was significantly higher in RH compared to moderate EH and NCS. [ABSTRACT FROM AUTHOR]

Published
2008

46. Pheochromocytoma as a catecholamine producing tumor: Implications for clinical practice.

Author

Zelinka, T., Eisenhofer, G., and Pacak, K.

Subjects
*PHEOCHROMOCYTOMA, *CATECHOLAMINES, *TUMORS, *ADRENERGIC receptors, *HUMAN chromosome abnormality diagnosis, *LAPAROSCOPIC surgery
Abstract

Pheochromocytomas are catecholamine-producing tumors presenting with various clinical symptoms, but mostly with headache, sweating, palpitations and hypertension. If not properly diagnosed, secretion of catecholamines may lead to fatal cardiovascular consequences. Biochemical testing for pheochromocytoma should be performed not only in symptomatic subjects or in subjects with adrenal incidentaloma but also in subjects with a genetic predisposition for pheochromocytoma (multiple endocrine neoplasia type 2, Von Hippel-Lindau (VHL) syndrome, neurofibromatosis type 1 (NF 1)and mutations of succinate dehydrogenase (SDH) genes). Once a pheochromocytoma is proven, computed tomography (CT), magnetic resonance imaging (MRI) and functional imaging with [123I]-MIBG may be used for tumor localization. Adequate medical pre-treatment is essential for successful operation which is performed in most cases by laparoscopy. After tumor removal, further follow-up is necessary due to possible recurrence. Although prognosis after tumor resection is excellent, a significant proportion of pheochromocytomas recur, some as metastases. Thus, appropriate follow-up is mandatory. [ABSTRACT FROM AUTHOR]

Published
2007
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47. Biochemical Markers of Endothelial Dysfunction in Patients with Endocrine and Essential Hypertension.

Author

Petrák, O., Widimský Jr., J., Zelinka, T., Kvasnička, J., Štrauch, B., Holaj, R., Štulc, T., Kvasnička, T., Bílková, J., and Škrha, J.

Subjects
BIOMARKERS, HYPERTENSION, VASOCONSTRICTORS, HYPERALDOSTERONISM, PHEOCHROMOCYTOMA, VON Willebrand factor, PLASMINOGEN activators, BLOOD pressure
Abstract

The aim of our study was to evaluate potential differences in the concentration of biochemical markers of endothelial dysfunction between essential hypertension, endocrine hypertension (pheochromocytoma, primary hyperaldosteronism) and control healthy group and to assess a potential relationship between these markers of endothelial dysfunction and vasopressor substances overproduced in endocrine hypertension. We have investigated 21 patients with moderate essential hypertension, 29 patients with primary hyperaldosteronism, 24 subjects with pheochromocytoma and 26 healthy volunteers. Following parameters of endothelial dysfunction were measured, von Willebrand factor (vWf), plasminogen activator (t-PA) and E-selectin (E-sel). Clinical blood pressure was measured according to the European Society of Hypertension recommendations. We found significantly higher levels of the von Willebrand factor in patients with essential hypertension in comparison with a control group (114±20 IU/dl vs 90±47 IU/dl; P=0.04) and patients with primary hyperaldosteronism (114±20 IU/dl vs 99±11 IU/dl; P=0.01). Patients with endocrine hypertension revealed increased levels of vWF compared to the control group, but these differences did not reach statistical significance. Levels of t-PA were increased in patients with pheochromocytoma in comparison with the control group (4.6±1.9 ng/ml vs 3.4±0.9 ng/ml; P=0.01) and with primary hyperaldosteronism (4.6±1.9 ng/ml vs 3.4±1.1 ng/ml; P<0.01). In case of E-selectin we found lower levels in patients with pheochromocytoma in comparison with other groups, but they differed significantly only with primary hyperaldosteronism (40.2±15.0 ng/ml vs 51.3±23.0 ng/ml; P=0.05). Our study did not reveal any convincing evidence of differences in the levels of biochemical markers of endothelial dysfunction between essential and endocrine hypertension. No correlation between the biochemical markers of endothelial dysfunction and vasopressor substances activated in endocrine hypertension was found. [ABSTRACT FROM AUTHOR]

Published
2006
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48. Impact of essential hypertension and primary aldosteronism on plasma brain natriuretic peptide concentration.

Author

Jakubik, P., Janota, T., Widimsky, J., Zelinka, T., Strauch, B., Petrak, O., Benakova, H., Bezdickova, D., Wichterle, D., Zima, T., and Hradec, J.

Subjects
HYPERTENSION, HYPERALDOSTERONISM, DIAGNOSIS, HEART failure, ATRIAL natriuretic peptides, BLOOD pressure
Abstract

Introduction. Brain natriuretic peptide (BNP) has important role in the diagnosis and management of heart failure. Data on the impact of blood pressure (BP) on BNP are controversial. In primary aldosteronism (PA), BNP production can be affected by both hypertension and specific endocrine mechanisms. This study was aimed at investigating the impact of hypertension and hyperaldosteronism on plasma BNP levels. Methods. Plasma BNP concentration, casual and 24-h BP and echocardiographic indices were assessed in 40 patients with moderate to severe essential hypertension (EH), 40 BP-matched patients with PA, and 40 age- and sex-matched healthy controls. Results. BNP levels in PA and EH groups did not differ significantly and were higher compared with those in controls [median and interquartile range 26 (13–48) pg/ml, p = 0.01, and 23 (9–32) pg/ml, n.s., vs 14 (6–26) pg/ml in controls]. Remarkably elevated BNP was observed only in three PA and two EH patients, all having significant left ventricular (LV) hypertrophy. BNP levels in PA and EH groups correlated weakly with casual and 24-h BP, interventricular septal thickness and LV mass index (LVMI). Diastolic BP and LVMI were identified as the strongest independent determinants of BNP (p = 0.002 and p = 0.01, respectively). Conclusions. Both PA and EH patients had modest and mutually comparable elevation of BNP, which was independently determined by diastolic BP and LVMI. Both subtypes of PA (aldosterone-producing adenoma and bilateral adrenal hyperplasia) had similar effect on BNP production. Specific impact of hyperaldosteronism on BNP was not confirmed. [ABSTRACT FROM AUTHOR]

Published
2006
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