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204 results on '"Lyden D"'

1. Molecular and physiologic changes in the SpaceX Inspiration4 civilian crew

Author

Jones, C. W., primary, Overbey, E. G., additional, Lacombe, J., additional, Ecker, A. J., additional, Meydan, C., additional, Ryon, K., additional, Tierney, B., additional, Damle, N., additional, MacKay, M., additional, Afshin, E. E., additional, Foox, J., additional, Park, J., additional, Nelson, T., additional, Suhail, M., additional, Byhaqui, S. G., additional, Aslam, B., additional, Tali, U. A., additional, Nisa, L., additional, Menon, P., additional, Patel, C. O., additional, Khan, S. A., additional, Ebert, D. J., additional, Everson, A., additional, Schubert, M. C., additional, Ali, N. N., additional, Sarma, M. S., additional, Kim, J., additional, Houerbi, N., additional, Grigorev, K., additional, Garcia Medina, S., additional, Summers, A. J., additional, Gu, J., additional, Altin, J. A., additional, Fattahi, A., additional, Hirzallah, M. I., additional, Wu, J. H., additional, Stahn, A. C., additional, Beheshti, A., additional, Klotz, R., additional, Ortiz, V., additional, Yu, M., additional, Patras, L., additional, Matei, I., additional, Lyden, D., additional, Melnick, A., additional, Banerjee, N., additional, Mullane, S., additional, Kleinman, A., additional, Loesche, M., additional, Menon, A. S., additional, Donoviel, D. B., additional, Urquieta, E., additional, Mateus, J., additional, Sargsyan, A. E., additional, Shelhamer, M., additional, Zenhausern, F., additional, Bershad, E. M., additional, Basner, M., additional, and Mason, C. E., additional

Published
2024
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5. In the News

Author

Leroy, E., Sicardy, B., Rafii, S., Lyden, D., Silliman, B. R., Lin, Cheng-Hornq, and Shumyatsky, G. Stathmin

Published
2006

6. 84TiP Predictive value of exosomes for therapy response in resectable/borderline resectable pancreatic cancer patients

Author

Cazacu, I.M., primary, Croitoru, V.M., additional, Paul, D., additional, Popa, E., additional, Matei, I., additional, Gheorghe, C., additional, Herlea, V., additional, Diculescu, M., additional, Bogdan, D., additional, Sandra, I., additional, Gramaticu, I-M., additional, Luca, N.I., additional, Dinu, I.M., additional, Alexandrescu, S., additional, Sorop, A., additional, Croitoru, A.E., additional, Dima, S., additional, Popescu, I., additional, and Lyden, D., additional

Published
2021
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12. Prognostic value of medulloblastoma extent of resection after accounting for molecular subgroup: a retrospective integrated clinical and molecular analysis

Author

Thompson, EM, Hielscher, T, Bouffet, E, Remke, M, Luu, B, Gururangan, S, McLendon, RE, Bigner, DD, Lipp, ES, Perreault, S, Cho, YJ, Grant, G, Kim, SK, Lee, JY, Rao, AAN, Giannini, C, Li, KKW, Ng, HK, Yao, Y, Kumabe, T, Tominaga, T, Grajkowska, WA, Perek-Polnik, M, Low, DCY, Seow, WT, Chang, KTE, Mora, J, Pollack, IF, Hamilton, RL, Leary, S, Moore, AS, Ingram, WJ, Hallahan, AR, Jouvet, A, Fèvre-Montange, M, Vasiljevic, A, Faure-Conter, C, Shofuda, T, Kagawa, N, Hashimoto, N, Jabado, N, Weil, AG, Gayden, T, Wataya, T, Shalaby, T, Grotzer, M, Zitterbart, K, Sterba, J, Kren, L, Hortobágyi, T, Klekner, A, László, B, Pócza, T, Hauser, P, Schüller, U, Jung, S, Jang, WY, French, PJ, Kros, JM, van Veelen, MLC, Massimi, L, Leonard, JR, Rubin, JB, Vibhakar, R, Chambless, LB, Cooper, MK, Thompson, RC, Faria, CC, Carvalho, A, Nunes, S, Pimentel, J, Fan, X, Muraszko, KM, López-Aguilar, E, Lyden, D, Garzia, L, Shih, DJH, Kijima, N, Schneider, C, Adamski, J, Northcott, PA, Kool, M, Jones, DTW, Chan, JA, Nikolic, A, Garre, ML, Van Meir, EG, Osuka, S, Olson, JJ, Jahangiri, A, and Castro, BA

Subjects
Adult, Male, Canada, Brain Neoplasms, Infant, Prognosis, Magnetic Resonance Imaging, Combined Modality Therapy, Disease-Free Survival, Child, Preschool, Disease Progression, Humans, Female, Child, Medulloblastoma, Retrospective Studies
Abstract

© 2016 Elsevier Ltd Background Patients with incomplete surgical resection of medulloblastoma are controversially regarded as having a marker of high-risk disease, which leads to patients undergoing aggressive surgical resections, so-called second-look surgeries, and intensified chemoradiotherapy. All previous studies assessing the clinical importance of extent of resection have not accounted for molecular subgroup. We analysed the prognostic value of extent of resection in a subgroup-specific manner. Methods We retrospectively identified patients who had a histological diagnosis of medulloblastoma and complete data about extent of resection and survival from centres participating in the Medulloblastoma Advanced Genomics International Consortium. We collected from resections done between April, 1997, and February, 2013, at 35 international institutions. We established medulloblastoma subgroup affiliation by gene expression profiling on frozen or formalin-fixed paraffin-embedded tissues. We classified extent of resection on the basis of postoperative imaging as gross total resection (no residual tumour), near-total resection (30 Gy vs no craniospinal irradiation). The primary analysis outcome was the effect of extent of resection by molecular subgroup and the effects of other clinical variables on overall and progression-free survival. Findings We included 787 patients with medulloblastoma (86 with WNT tumours, 242 with SHH tumours, 163 with group 3 tumours, and 296 with group 4 tumours) in our multivariable Cox models of progression-free and overall survival. We found that the prognostic benefit of increased extent of resection for patients with medulloblastoma is attenuated after molecular subgroup affiliation is taken into account. We identified a progression-free survival benefit for gross total resection over sub-total resection (hazard ratio [HR] 1·45, 95% CI 1·07–1·96, p=0·16) but no overall survival benefit (HR 1·23, 0·87–1·72, p=0·24). We saw no progression-free survival or overall survival benefit for gross total resection compared with near-total resection (HR 1·05, 0·71–1·53, p=0·8158 for progression-free survival and HR 1·14, 0·75–1·72, p=0·55 for overall survival). No significant survival benefit existed for greater extent of resection for patients with WNT, SHH, or group 3 tumours (HR 1·03, 0·67–1·58, p=0·89 for sub-total resection vs gross total resection). For patients with group 4 tumours, gross total resection conferred a benefit to progression-free survival compared with sub-total resection (HR 1·97, 1·22–3·17, p=0·0056), especially for those with metastatic disease (HR 2·22, 1·00–4·93, p=0·050). However, gross total resection had no effect on overall survival compared with sub-total resection in patients with group 4 tumours (HR 1·67, 0·93–2·99, p=0·084). Interpretation The prognostic benefit of increased extent of resection for patients with medulloblastoma is attenuated after molecular subgroup affiliation is taken into account. Although maximum safe surgical resection should remain the standard of care, surgical removal of small residual portions of medulloblastoma is not recommended when the likelihood of neurological morbidity is high because there is no definitive benefit to gross total resection compared with near-total resection. Funding Canadian Cancer Society Research Institute, Terry Fox Research Institute, Canadian Institutes of Health Research, National Institutes of Health, Pediatric Brain Tumor Foundation, and the Garron Family Chair in Childhood Cancer Research.

Published
2016

14. Proteomic evaluation of biliary exosomes implicates exportin7 in the pathogenesis of extrahepatic cholangiocarcinoma

Author

Hernandez, J., primary, Doussot, A., additional, Zheng, J., additional, Tesic Mark, M., additional, Molina, H., additional, Costa da Silva, B., additional, van Beek, E., additional, Bojmar, L., additional, Sinha, S., additional, Allen, P., additional, DeMatteo, R., additional, D'Angelica, M., additional, Kingham, T.P., additional, Lyden, D., additional, and Jarnagin, W., additional

Published
2017
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15. Prognostic value of medulloblastoma extent of resection after accounting for molecular subgroup: A retrospective integrated clinical and molecular analysis

Author

Thompson, E.M. (Eric M.), Hielscher, T. (Thomas), Bouffet, E. (Eric), Remke, M. (Marc), Luu, P. (Phan), Gururangan, S. (Sridharan), McLendon, R.E. (Roger E.), Bigner, D.D. (Darell), Lipp, E.S. (Eric S.), Perreault, S. (Sebastien), Cho, Y.-J. (Yoon-Jae), Grant, G. (Gerald), Kim, S.-K. (Seung-Ki), Lee, J.Y. (Ji Yeoun), Rao, A.A.N. (Amulya A. Nageswara), Giannini, C. (Caterina), Li, K.K.W. (Kay Ka Wai), Ng, H.-K. (Ho-Keung), Yao, Y. (Yu), Kumabe, T. (Toshihiro), Tominaga, T. (Teiji), Grajkowska, W.A. (Wieslawa), Perek-Polnik, M. (Marta), Low, D.C.Y. (David C.Y.), Seow, W.T. (Wan Tew), Chang, K.T.E. (Kenneth T.E.), Mora, J. (Jaume), Pollack, A. (Aaron), Hamilton, R.L. (Ronald L.), Leary, S. (Sarah), Moore, A.S. (Andrew S.), Ingram, W.J. (Wendy J.), Hallahan, A.R. (Andrew R.), Jouvet, A. (Anne), Fèvre-Montange, M. (Michelle), Vasiljevic, A. (Alexandre), Faure-Conter, C. (Cecile), Shofuda, T. (Tomoko), Kagawa, N. (Naoki), Hashimoto, N. (Naoya), Jabado, N. (Nada), Weil, A.G. (Alexander G.), Gayden, T. (Tenzin), Wataya, T. (Takafumi), Shalaby, T. (Tarek), Grotzer, M. (Michael), Zitterbart, K. (Karel), Sterba, J., Kren, L. (Leos), Hortobágyi, T. (Tibor), Klekner, A. (Almos), Bognár, L. (László), Pócza, T. (Tímea), Hauser, P. (Peter), Schüller, U. (Ulrich), Jung, S. (Shin), Jang, W.-Y. (Woo-Youl), French, P.J. (Pim), Kros, J.M. (Johan), Veelen-Vincent, M.L.C. (Marie-Lise) van, Massimi, L. (Luca), Leonard, J.R. (Jeffrey), Rubin, J.B. (Joshua), Vibhakar, R. (Rajeev), Chambless, L.B. (Lola B.), Cooper, M.K. (Michael), Thompson, R.C. (Reid), Faria, R. (Rui), Carvalho, A. (Alice), Nunes, S. (Sofia), Pimentel, J., Fan, X. (Xing), Muraszko, K.M. (Karin), López-Aguilar, E. (Enrique), Lyden, D. (David), Garzia, L. (Livia), Shih, D.J.H. (David J.), Kijima, N. (Noriyuki), Schneider, C. (Christian), Adamski, J. (Jennifer), Northcott, P.A. (Paul A.), Kool, M. (Marcel), Jones, D. (David), Chan, J.A. (Jennifer A.), Nikolic, A. (Ana), Garre, M.L. (Maria Luisa), Van Meir, E.G. (Erwin G.), Osuka, S. (Satoru), Olson, J.J. (Jeffrey J.), Jahangiri, A. (Arman), Castro, B.A. (Brandyn A.), Gupta, N. (Nalin), Weiss, W.A. (William A.), Moxon-Emre, I. (Iska), Mabbott, D.J. (Donald J.), Lassaletta, A. (Alvaro), Hawkins, C.E. (Cynthia), Tabori, U. (Uri), Drake, J. (James), Kulkarni, A. (Abhaya), Dirks, M. (Maaike), Rutka, J.T. (James), Korshunov, A. (Andrey), Pfister, S.M. (Stefan), Packer, R.J. (Roger J.), Ramaswamy, E.A., Taylor, M.D. (Michael), Thompson, E.M. (Eric M.), Hielscher, T. (Thomas), Bouffet, E. (Eric), Remke, M. (Marc), Luu, P. (Phan), Gururangan, S. (Sridharan), McLendon, R.E. (Roger E.), Bigner, D.D. (Darell), Lipp, E.S. (Eric S.), Perreault, S. (Sebastien), Cho, Y.-J. (Yoon-Jae), Grant, G. (Gerald), Kim, S.-K. (Seung-Ki), Lee, J.Y. (Ji Yeoun), Rao, A.A.N. (Amulya A. Nageswara), Giannini, C. (Caterina), Li, K.K.W. (Kay Ka Wai), Ng, H.-K. (Ho-Keung), Yao, Y. (Yu), Kumabe, T. (Toshihiro), Tominaga, T. (Teiji), Grajkowska, W.A. (Wieslawa), Perek-Polnik, M. (Marta), Low, D.C.Y. (David C.Y.), Seow, W.T. (Wan Tew), Chang, K.T.E. (Kenneth T.E.), Mora, J. (Jaume), Pollack, A. (Aaron), Hamilton, R.L. (Ronald L.), Leary, S. (Sarah), Moore, A.S. (Andrew S.), Ingram, W.J. (Wendy J.), Hallahan, A.R. (Andrew R.), Jouvet, A. (Anne), Fèvre-Montange, M. (Michelle), Vasiljevic, A. (Alexandre), Faure-Conter, C. (Cecile), Shofuda, T. (Tomoko), Kagawa, N. (Naoki), Hashimoto, N. (Naoya), Jabado, N. (Nada), Weil, A.G. (Alexander G.), Gayden, T. (Tenzin), Wataya, T. (Takafumi), Shalaby, T. (Tarek), Grotzer, M. (Michael), Zitterbart, K. (Karel), Sterba, J., Kren, L. (Leos), Hortobágyi, T. (Tibor), Klekner, A. (Almos), Bognár, L. (László), Pócza, T. (Tímea), Hauser, P. (Peter), Schüller, U. (Ulrich), Jung, S. (Shin), Jang, W.-Y. (Woo-Youl), French, P.J. (Pim), Kros, J.M. (Johan), Veelen-Vincent, M.L.C. (Marie-Lise) van, Massimi, L. (Luca), Leonard, J.R. (Jeffrey), Rubin, J.B. (Joshua), Vibhakar, R. (Rajeev), Chambless, L.B. (Lola B.), Cooper, M.K. (Michael), Thompson, R.C. (Reid), Faria, R. (Rui), Carvalho, A. (Alice), Nunes, S. (Sofia), Pimentel, J., Fan, X. (Xing), Muraszko, K.M. (Karin), López-Aguilar, E. (Enrique), Lyden, D. (David), Garzia, L. (Livia), Shih, D.J.H. (David J.), Kijima, N. (Noriyuki), Schneider, C. (Christian), Adamski, J. (Jennifer), Northcott, P.A. (Paul A.), Kool, M. (Marcel), Jones, D. (David), Chan, J.A. (Jennifer A.), Nikolic, A. (Ana), Garre, M.L. (Maria Luisa), Van Meir, E.G. (Erwin G.), Osuka, S. (Satoru), Olson, J.J. (Jeffrey J.), Jahangiri, A. (Arman), Castro, B.A. (Brandyn A.), Gupta, N. (Nalin), Weiss, W.A. (William A.), Moxon-Emre, I. (Iska), Mabbott, D.J. (Donald J.), Lassaletta, A. (Alvaro), Hawkins, C.E. (Cynthia), Tabori, U. (Uri), Drake, J. (James), Kulkarni, A. (Abhaya), Dirks, M. (Maaike), Rutka, J.T. (James), Korshunov, A. (Andrey), Pfister, S.M. (Stefan), Packer, R.J. (Roger J.), Ramaswamy, E.A., and Taylor, M.D. (Michael)

Abstract

Background: Patients with incomplete surgical resection of medulloblastoma are controversially regarded as having a marker of high-risk disease, which leads to patients undergoing aggressive surgical resections, so-called second-look surgeries, and intensified chemoradiotherapy. All previous studies assessing the clinical importance of extent of resection have not accounted for molecular subgroup. We analysed the prognostic value of extent of resection in a subgroup-specific manner. Methods: We retrospectively identified patients who had a histological diagnosis of medulloblastoma and complete data about extent of resection and survival from centres participating in the Medulloblastoma Advanced Genomics International Consortium. We collected from resections done between April, 1997, and February, 2013, at 35 international institutions. We established medulloblastoma subgroup affiliation by gene expression profiling on frozen or formalin-fixed paraffin-embedded tissues. We classified extent of resection on the basis of postoperative imaging as gross total resection (no residual tumour), near-total resection (<1·5 cm2 tumour remaining), or sub-total resection (≥1·5 cm2 tumour remaining). We did multivariable analyses of overall survival and progression-free survival using the variables molecular subgroup (WNT, SHH, group 4, and group 3), age (<3 vs ≥3 years old), metastatic status (metastases vs no metastases), geographical location of therapy (North America/Australia vs rest of the world), receipt of chemotherapy (yes vs no) and receipt of craniospinal irradiation (<30 Gy or >30 Gy vs no craniospinal irradiation). The primary analysis outcome was the effect of extent of resection by molecular subgroup and the effects of other clinical variables on overall and progression-free survival. Findings: We included 787 patients with medulloblastoma (86 with WNT tumours, 242 with SHH tumours, 163 with group 3 tumours, and 296 with group 4 tumours) in our multivariable Cox mod

Published
2016
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20. LAB-ANGIOGENESIS AND INVASION

Author

Proescholdt, M. A., primary, Merrill, M. J., additional, Stoerr, E.-M., additional, Lohmeier, A., additional, Brawanski, A., additional, Sim, H., additional, Hu, B., additional, Pineda, C. A., additional, Yoon, S.-O., additional, Viapiano, M. S., additional, Rajappa, P., additional, Cobb, W. S., additional, Huang, Y., additional, Lyden, D. C., additional, Bromberg, J., additional, Greenfield, J. P., additional, Li, M., additional, Mukasa, A., additional, Inda, M. d.-M., additional, Zhang, J., additional, Chin, L., additional, Cavenee, W., additional, Furnari, F., additional, Zheng, P.-P., additional, van der Weiden, M., additional, van der Spek, P. J., additional, Vincent, A. J., additional, Kros, J. M., additional, Fathallah-Shaykh, H. M., additional, Saut, O., additional, Lagaert, J.-B., additional, Colin, T., additional, Araysi, L., additional, Tang, Z., additional, Duck, K. A., additional, Ponnuru, P., additional, Neely, E. B., additional, Connor, J. R., additional, Esencay, M., additional, Gonzalez, P., additional, Gaziel, A., additional, Safraz, Y., additional, Mira, H., additional, Hernando, E., additional, Zagzag, D., additional, McDermott, R. A., additional, Ulasov, I., additional, Kaverina, N., additional, Gabikian, P., additional, Lesniak, M., additional, Iranmahboob, A., additional, Haber, M., additional, Fatterpekar, G., additional, Raz, E., additional, Placantonakis, D., additional, Eoli, M., additional, Rabascio, C., additional, Cuppini, L., additional, Anghileri, E., additional, Pellegatta, S., additional, Calleri, A., additional, Mancuso, P., additional, Porrati, P., additional, Bertolini, F., additional, Finocchiaro, G., additional, Seals, D. F., additional, Burger, K. L., additional, Gibo, D. M., additional, Debinski, W., additional, Tran, N. L., additional, Tuncali, S., additional, Kloss, J., additional, Yang, Z., additional, Schumacher, C. A., additional, Diegel, C., additional, Ross, J. T., additional, Williams, B. O., additional, Eschbacher, J. M., additional, Loftus, J. C., additional, Whiteman, M., additional, Dombovy-Johnson, M., additional, Vangellow, A., additional, Liu, Y., additional, Carson-Walter, E., additional, Walter, K. A., additional, Walter, K., additional, Cortes-Santiago, N., additional, Gabrusiewicz, K., additional, Liu, D., additional, Hossain, M. B., additional, Gumin, J., additional, Fan, X., additional, Conrad, C., additional, Aldape, K., additional, Gilbert, M., additional, Raghunathan, A., additional, Yung, W. K. A., additional, Fueyo, J., additional, Gomez-Manzano, C., additional, Bae, E., additional, Huang, P., additional, Burgett, M., additional, Muller-Greven, G., additional, Kar, N., additional, Gladson, C. L., additional, Engler, J. R., additional, Robinson, A. E., additional, Molinaro, A., additional, Phillips, J. J., additional, Zadeh, G., additional, Burrell, K., additional, Hill, R., additional, Piao, Y., additional, Liang, J., additional, Henry, V., additional, Holmes, L., additional, Sulman, E., additional, deGroot, J. F., additional, de Groot, J. F., additional, Rong, W., additional, Funato, K., additional, Georgala, P., additional, Shimizu, F., additional, Droms, L., additional, Tabar, V., additional, Parker, J. J., additional, Dionne, K. R., additional, Massarwa, R., additional, Klaassen, M., additional, Foreman, N. K., additional, Niswander, L., additional, Canoll, P., additional, Kleinschmidt-DeMasters, B. K., additional, and Waziri, A., additional

Published
2012
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21. DIFFUSE INTRINSIC PONTINE GLIOMA (DIPG)

Author

Zaghloul, M., primary, Ahmed, S., additional, Eldebaway, E., additional, Mousa, A., additional, Amin, A., additional, Elkhateeb, N., additional, Sabry, M., additional, Ogiwara, H., additional, Morota, N., additional, Sufit, A., additional, Donson, A., additional, Birks, D., additional, Patel, P., additional, Foreman, N., additional, Handler, M., additional, Massimino, M., additional, Biassoni, V., additional, Gandola, L., additional, Schiavello, E., additional, Pecori, E., additional, Potepan, P., additional, Bach, F., additional, Janssens, G. O., additional, Jansen, M. H., additional, Lauwers, S. J., additional, Nowak, P. J., additional, Oldenburger, F. R., additional, Bouffet, E., additional, Saran, F., additional, van Ulzen, K. K., additional, van Lindert, E. J., additional, Schieving, J. H., additional, Boterberg, T., additional, Kaspers, G. J., additional, Span, P. N., additional, Kaanders, J. H., additional, Gidding, C. E., additional, Hargrave, D., additional, Bailey, S., additional, Howman, A., additional, Pizer, B., additional, Harris, D., additional, Jones, D., additional, Kearns, P., additional, Picton, S., additional, Wheatley, K., additional, Gibson, M., additional, Glaser, A., additional, Connolly, D., additional, Kawamura, A., additional, Nagashima, T., additional, Yamamoto, K., additional, Sakata, J., additional, Lober, R., additional, Freret, M., additional, Fisher, P., additional, Edwards, M., additional, Yeom, K., additional, Monje, M., additional, Jansen, M., additional, Aliaga, E. S., additional, Van Der Hoeven, E., additional, Van Vuurden, D., additional, Heymans, M., additional, Gidding, C., additional, De Bont, E., additional, Reddingius, R., additional, Peeters-Scholte, C., additional, van Meeteren, A. S., additional, Gooskens, R., additional, Granzen, B., additional, Paardekoper, G., additional, Janssens, G., additional, Noske, D., additional, Barkhof, F., additional, Vandertop, W. P., additional, Kaspers, G., additional, Saratsis, A., additional, Yadavilli, S., additional, Nazarian, J., additional, Mitra, S., additional, Mallick, S., additional, Kim, J., additional, Beachy, P., additional, Nobre, L., additional, Vasconcelos, F., additional, Lima, F., additional, Mattos, D., additional, Kuiven, N., additional, Lima, G., additional, Silveira, J., additional, Sevilha, M., additional, Lima, M. A., additional, Ferman, S., additional, Leblond, P., additional, Lansiaux, A., additional, Rialland, X., additional, Gentet, J.-C., additional, Geoerger, B., additional, Frappaz, D., additional, Aerts, I., additional, Bernier-Chastagner, V., additional, Shah, R., additional, Zaky, W., additional, Grimm, J., additional, Bluml, S., additional, Wong, K., additional, Dhall, G., additional, Caretti, V., additional, Schellen, P., additional, Lagerweij, T., additional, Bugiani, M., additional, Navis, A., additional, Wesseling, P., additional, Noske, D. P., additional, Wurdinger, T., additional, Lee, H., additional, Ziegler, D., additional, Schroeder, K., additional, Huang, E., additional, Berlow, N., additional, Patel, R., additional, Becher, O., additional, Taylor, I., additional, Mao, X.-g., additional, Hutt, M., additional, Weingart, M., additional, Kahlert, U., additional, Maciacyk, J., additional, Nikkhah, G., additional, Eberhart, C., additional, Raabe, E., additional, Barton, K., additional, Misuraca, K., additional, Zhou, Z., additional, Rotman, L., additional, Ho, S., additional, Souweidane, M., additional, Lim, K. J., additional, Warren, K., additional, Chang, H., additional, Lightner, D., additional, Haque, S., additional, Khakoo, Y., additional, Dunkel, I., additional, Gilheeney, S., additional, Kramer, K., additional, Lyden, D., additional, Wolden, S., additional, Greenfield, J., additional, De Braganca, K., additional, Ting-Rong, H., additional, Muh-Li, L., additional, Kai-Ping, C., additional, Tai-Tong, W., additional, Hsin-Hung, C., additional, Kebudi, R., additional, Cakir, F. B., additional, Agaoglu, F. Y., additional, Gorgun, O., additional, Dizdar, Y., additional, Ayan, I., additional, Darendeliler, E., additional, Zapotocky, M., additional, Churackova, M., additional, Malinova, B., additional, Kodet, R., additional, Kyncl, M., additional, Tichy, M., additional, Stary, J., additional, Sumerauer, D., additional, Minturn, J., additional, Shu, H.-K., additional, Fisher, M., additional, Patti, R., additional, Janss, A., additional, Allen, J., additional, Phillips, P., additional, Belasco, J., additional, Taylor, K., additional, Baudis, M., additional, von Beuren, A., additional, Fouladi, M., additional, and Jones, C., additional

Published
2012
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25. Corrigendum: Cytokine-mediated deployment of SDF-1 induces revascularization through recruitment of CXCR4+ hemangiocytes

Author

Jin, D K, Shido, K, Kopp, H-G, Petit, I, Shmelkov, S V, Young, L M, Hooper, A T, Amano, H, Avecilla, S T, Heissig, B, Hattori, K, Zhang, F, Hicklin, D J, Wu, Y, Zhu, Z, Dunn, A, Salari, H, Werb, Z, Hackett, N R, Crystal, R G, Lyden, D, and Rafii, S

Abstract

Author(s): D K Jin; K Shido; H-G Kopp; I Petit; S V Shmelkov; L M Young; A T Hooper; H Amano; S T Avecilla; B Heissig; K Hattori; F Zhang; [...]

Published
2006
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27. Intensive chemotherapy and bone marrow rescue for young children with newly diagnosed malignant brain tumors.

Author

Mason, W P, primary, Grovas, A, additional, Halpern, S, additional, Dunkel, I J, additional, Garvin, J, additional, Heller, G, additional, Rosenblum, M, additional, Gardner, S, additional, Lyden, D, additional, Sands, S, additional, Puccetti, D, additional, Lindsley, K, additional, Merchant, T E, additional, O'Malley, B, additional, Bayer, L, additional, Petriccione, M M, additional, Allen, J, additional, and Finlay, J L, additional

Published
1998
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28. #662 Taxol induces wide-spread necrosis in rhabdomyosarcoma

Author

Lyden, D., primary, Fernandez, J. M., additional, Manova, K., additional, Gerald, W., additional, Whitty, K. Blease, additional, Saenz, N., additional, Ghavimi, F., additional, Jen, Y., additional, Finlay, J., additional, O'Reilly, R., additional, and Benezra, R., additional

Published
1997
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29. Coxsackievirus B-3-induced myocarditis. Effect of sex steroids on viremia and infectivity of cardiocytes

Author

Lyden, D. C., Olszewski, J., Feran, M., Job, L. P., and Huber, S. A.

Subjects
Male, Mice, Inbred BALB C, viruses, virus diseases, Coxsackievirus Infections, Heart, Enterovirus B, Human, Mice, Myocarditis, Sex Factors, Cytopathogenic Effect, Viral, Animals, Female, Endothelium, Viremia, Gonadal Steroid Hormones, Research Article
Abstract

Male and female BALB/c mice were inoculated with various concentrations of coxsackievirus, group B, type 3 (CVB3), ranging from 10 to 10(7) plaque-forming units (PFU). Lower viral doses (greater than 10(2) PFU) induced severe myocarditis in male mice but caused little injury in females. With 10(7) PFU, females also developed severe disease. Females may be relatively resistant to CVB3-induced myocarditis because virus entry into the blood and heart is less effective. Males given 125I-CVB3 show approximately 2-4 and 20-fold more radioactivity in the peripheral blood and heart, respectively, than females. No differences were observed between the sexes in 125I-bovine serum albumin penetration. Sex steroid hormones influence viremia and virus localization; females given exogenous testosterone and progesterone demonstrate ten times more virus in their hearts than animals given estradiol. The hormones may act by increasing virus receptor expression on endothelial cells and myocytes.

Published
1987

30. Influence of sex hormones on coxsackie virus group B, type 3 induced myocarditis in Balb/c mice.

Author

Lyden, D., Olsewski, J., and Huber, S.A.

Abstract

Susceptibility to coxsackie virus group B, type 3 (CVB3) induced myocarditis changes with age. Very young (< 4 weeks) Balb/c mice show minimal cardiac injury after infection, while young adult males (6–12 weeks) develop severe myocarditis. Age-matched females remain largely protected. As the mice continue to age, susceptibility in females gradually increases while that in males decreases, ultimately resulting in equal myocardial damage between the sexes by 40 weeks of age. Enhanced myocarditis in old females correlates withincreased humoral and cellular immunity to the virus and heart antigens and results from decreased oestrogen levels in these animals. [ABSTRACT FROM PUBLISHER]

Published
1987
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41. A Genetic Approach to Understanding Tumor Angiogenesis.

Author

Benezra, R., de Candia, P., Li, H., Romero, E., Lyden, D., Rafii, S., and Ruzinova, M.

Subjects
*ANTINEOPLASTIC agents, *NEOVASCULARIZATION inhibitors, *TUMORS, *PROTEINS, *ENDOTHELIUM, *LABORATORY mice
Abstract

Proposes a genetic approach to the understanding of the effects of antiangiogenesis on tumor growth in mouse models. Basic biology of the Id proteins; Role of the Id proteins in the mobilization of bone-marrow-derived endothelial precursors; Prospects for targeting Id proteins as a means of inhibiting tumor angiogenesis.

Published
2002
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42. Prognostic value of medulloblastoma extent of resection after accounting for molecular subgroup: a retrospective integrated clinical and molecular analysis

Author

Iska Moxon-Emre, Livia Garzia, Karin M. Muraszko, Thomas Hielscher, Satoru Osuka, Xing Fan, Andrew S. Moore, Toshihiro Kumabe, Betty Luu, Cynthia Hawkins, Tibor Hortobágyi, David T.W. Jones, Leos Kren, Sridharan Gururangan, Peter Hauser, Peter B. Dirks, David Shih, Jeffrey R. Leonard, Andrey Korshunov, Michael K. Cooper, Gerald A. Grant, Naoki Kagawa, Andrew R. Hallahan, Claudia C. Faria, Pim J. French, Donald J. Mabbott, Joshua B. Rubin, Jaume Mora, Sarah Leary, Michael A. Grotzer, Cécile Faure-Conter, Stefan M. Pfister, Erwin G. Van Meir, Rajeev Vibhakar, Bognár László, Shin Jung, Yoon Jae Cho, Reid C. Thompson, Nada Jabado, Alexander G. Weil, David C.Y. Low, Karel Zitterbart, Enrique López-Aguilar, Alice Carvalho, Kenneth Tou En Chang, Ho Keung Ng, Ana Nikolic, Eric M. Thompson, Jennifer A. Chan, James T. Rutka, Kay Ka Wai Li, Yu Yao, Paul A. Northcott, Vijay Ramaswamy, Roger E. McLendon, Wan Tew Seow, Wendy J. Ingram, Wiesława Grajkowska, Ronald L. Hamilton, Marcel Kool, Caterina Giannini, William A. Weiss, Luca Massimi, Ian F. Pollack, Marie Lise C. van Veelen, Jaroslav Sterba, David Lyden, Ji Yeoun Lee, Ulrich Schüller, Sébastien Perreault, Nalin Gupta, Johan M. Kros, Arman Jahangiri, Roger J. Packer, Brandyn A. Castro, Lola B. Chambless, Jeffrey J. Olson, Seung-Ki Kim, Almos Klekner, Woo Youl Jang, Uri Tabori, Michelle Fèvre-Montange, Marc Remke, Takafumi Wataya, Michael D. Taylor, Sofia Nunes, Marta Perek-Polnik, Tímea Pócza, Amulya A. Nageswara Rao, James M. Drake, Tenzin Gayden, Alexandre Vasiljevic, Eric S. Lipp, Christian Schneider, Alvaro Lassaletta, Jennifer Adamski, Tarek Shalaby, Darell D. Bigner, Teiji Tominaga, Naoya Hashimoto, Anne Jouvet, Abhaya V. Kulkarni, Noriyuki Kijima, Tomoko Shofuda, José Pimentel, Eric Bouffet, Maria Luisa Garrè, Thompson E.M., Hielscher T., Bouffet E., Remke M., Luu B., Gururangan S., McLendon R.E., Bigner D.D., Lipp E.S., Perreault S., Cho Y.-J., Grant G., Kim S.-K., Lee J.Y., Rao A.A.N., Giannini C., Li K.K.W., Ng H.-K., Yao Y., Kumabe T., Tominaga T., Grajkowska W.A., Perek-Polnik M., Low D.C.Y., Seow W.T., Chang K.T.E., Mora J., Pollack I.F., Hamilton R.L., Leary S., Moore A.S., Ingram W.J., Hallahan A.R., Jouvet A., Fevre-Montange M., Vasiljevic A., Faure-Conter C., Shofuda T., Kagawa N., Hashimoto N., Jabado N., Weil A.G., Gayden T., Wataya T., Shalaby T., Grotzer M., Zitterbart K., Sterba J., Kren L., Hortobagyi T., Klekner A., Laszlo B., Pocza T., Hauser P., Schuller U., Jung S., Jang W.-Y., French P.J., Kros J.M., van Veelen M.-L.C., Massimi L., Leonard J.R., Rubin J.B., Vibhakar R., Chambless L.B., Cooper M.K., Thompson R.C., Faria C.C., Carvalho A., Nunes S., Pimentel J., Fan X., Muraszko K.M., Lopez-Aguilar E., Lyden D., Garzia L., Shih D.J.H., Kijima N., Schneider C., Adamski J., Northcott P.A., Kool M., Jones D.T.W., Chan J.A., Nikolic A., Garre M.L., Van Meir E.G., Osuka S., Olson J.J., Jahangiri A., Castro B.A., Gupta N., Weiss W.A., Moxon-Emre I., Mabbott D.J., Lassaletta A., Hawkins C.E., Tabori U., Drake J., Kulkarni A., Dirks P., Rutka J.T., Korshunov A., Pfister S.M., Packer R.J., Ramaswamy V., Taylor M.D., Neurology, Pathology, and Neurosurgery

Subjects
Adult, Male, medicine.medical_specialty, Canada, medicine.medical_treatment, Klinikai orvostudományok, Article, Disease-Free Survival, Brain Neoplasm, 03 medical and health sciences, 0302 clinical medicine, Retrospective Studie, medicine, Humans, Child, Retrospective Studies, Medulloblastoma, Chemotherapy, Proportional hazards model, business.industry, Brain Neoplasms, Hazard ratio, Cancer, Infant, Retrospective cohort study, Orvostudományok, medicine.disease, Prognosis, Combined Modality Therapy, Magnetic Resonance Imaging, 3. Good health, Surgery, Radiation therapy, Oncology, 030220 oncology & carcinogenesis, Child, Preschool, Disease Progression, Female, business, 030217 neurology & neurosurgery, Chemoradiotherapy, Human
Abstract

BACKGROUND: Patients with incomplete surgical resection of medulloblastoma are controversially regarded as having a marker of high-risk disease, which leads to patients undergoing aggressive surgical resections, so-called second-look surgeries, and intensified chemoradiotherapy. All previous studies assessing the clinical importance of extent of resection have not accounted for molecular subgroup. We analysed the prognostic value of extent of resection in a subgroup-specific manner. METHODS: We retrospectively identified patients who had a histological diagnosis of medulloblastoma and complete data about extent of resection and survival from centres participating in the Medulloblastoma Advanced Genomics International Consortium. We collected from resections done between April, 1997, and February, 2013, at 35 international institutions. We established medulloblastoma subgroup affiliation by gene expression profiling on frozen or formalin-fixed paraffin-embedded tissues. We classified extent of resection on the basis of postoperative imaging as gross total resection (no residual tumour), near-total resection (30 Gy vs no craniospinal irradiation). The primary analysis outcome was the effect of extent of resection by molecular subgroup and the effects of other clinical variables on overall and progression-free survival. FINDINGS: We included 787 patients with medulloblastoma (86 with WNT tumours, 242 with SHH tumours, 163 with group 3 tumours, and 296 with group 4 tumours) in our multivariable Cox models of progression-free and overall survival. We found that the prognostic benefit of increased extent of resection for patients with medulloblastoma is attenuated after molecular subgroup affiliation is taken into account. We identified a progression-free survival benefit for gross total resection over sub-total resection (hazard ratio [HR] 1·45, 95% CI 1·07-1·96, p=0·16) but no overall survival benefit (HR 1·23, 0·87-1·72, p=0·24). We saw no progression-free survival or overall survival benefit for gross total resection compared with near-total resection (HR 1·05, 0·71-1·53, p=0·8158 for progression-free survival and HR 1·14, 0·75-1·72, p=0·55 for overall survival). No significant survival benefit existed for greater extent of resection for patients with WNT, SHH, or group 3 tumours (HR 1·03, 0·67-1·58, p=0·89 for sub-total resection vs gross total resection). For patients with group 4 tumours, gross total resection conferred a benefit to progression-free survival compared with sub-total resection (HR 1·97, 1·22-3·17, p=0·0056), especially for those with metastatic disease (HR 2·22, 1·00-4·93, p=0·050). However, gross total resection had no effect on overall survival compared with sub-total resection in patients with group 4 tumours (HR 1·67, 0·93-2·99, p=0·084). INTERPRETATION: The prognostic benefit of increased extent of resection for patients with medulloblastoma is attenuated after molecular subgroup affiliation is taken into account. Although maximum safe surgical resection should remain the standard of care, surgical removal of small residual portions of medulloblastoma is not recommended when the likelihood of neurological morbidity is high because there is no definitive benefit to gross total resection compared with near-total resection. FUNDING: Canadian Cancer Society Research Institute, Terry Fox Research Institute, Canadian Institutes of Health Research, National Institutes of Health, Pediatric Brain Tumor Foundation, and the Garron Family Chair in Childhood Cancer Research.

Published
2016

43. A genetic approach to understanding tumor angiogenesis

Author

H. Li, Shahin Rafii, E. Romero, David Lyden, Robert Benezra, P. De Candia, Marianna B. Ruzinova, Benezra, R., De Candia, P., Li, H., Romero, E., Lyden, D., Rafii, S., and Ruzinova, M.

Subjects
Tumor angiogenesis, Inhibitor of Differentiation Protein 1, Computational biology, Biology, Biochemistry, Mice, Text mining, Neoplasms, Genetics, Animals, Humans, Molecular Biology, Mice, Knockout, Vascular Endothelial Growth Factor Receptor-1, Models, Genetic, Neovascularization, Pathologic, business.industry, Neoplasms, Experimental, Hematopoietic Stem Cells, Vascular Endothelial Growth Factor Receptor-2, Neoplasm Proteins, Repressor Proteins, Gene Targeting, Inhibitor of Differentiation Proteins, Endothelium, Vascular, business, Transcription Factors
Published
2003

44. The IL-6/JAK/Stat3 Feed-Forward Loop Drives Tumorigenesis and Metastasis

Author

Mario Taffurelli, Qing Chang, David Lyden, Dennis Huszar, Rosandra N. Kaplan, Elisa de Stanchina, Selena Granitto, Jacqueline Bromberg, Xinmin Zhang, Norihiro Nishimoto, Jesse W. Cotari, Marjan Berishaj, Donatella Santini, Katia Manova, Massimiliano Bonafè, Grégoire Altan-Bonnet, Laura Daly, Ming O. Li, Sizhi Paul Gao, Larry Norton, Mary L. Alpaugh, Eirini Bournazou, Jared Wels, Till Martin Theilen, Claudio Ceccarelli, Pasquale Sansone, Chang Q, Bournazou E, Sansone P, Berishaj M, Gao SP, Daly L, Wels J, Theilen T, Granitto S, Zhang X, Cotari J, Alpaugh ML, de Stanchina E, Manova K, Li M, Bonafe M, Ceccarelli C, Taffurelli M, Santini D, Altan-Bonnet G, Kaplan R, Norton L, Nishimoto N, Huszar D, Lyden D, and Bromberg J

Subjects
0303 health sciences, Cancer Research, Tumor microenvironment, Angiogenesis, Biology, lcsh:Neoplasms. Tumors. Oncology. Including cancer and carcinogens, medicine.disease_cause, medicine.disease, lcsh:RC254-282, INTERLEUKIN 6, Metastasis, 03 medical and health sciences, 0302 clinical medicine, BREAST CANCER, Tumor progression, 030220 oncology & carcinogenesis, Cancer research, medicine, Myeloid-derived Suppressor Cell, STAT protein, Carcinogenesis, Janus kinase, 030304 developmental biology
Abstract

We have investigated the importance of interleukin-6 (IL-6) in promoting tumor growth and metastasis. In human primary breast cancers, increased levels of IL-6 were found at the tumor leading edge and positively correlated with advanced stage, suggesting a mechanistic link between tumor cell production of IL-6 and invasion. In support of this hypothesis, we showed that the IL-6/Janus kinase (JAK)/signal transducer and activator of transcription 3 (Stat3) pathway drives tumor progression through the stroma and metastatic niche. Overexpression of IL-6 in tumor cell lines promoted myeloid cell recruitment, angiogenesis, and induced metastases. We demonstrated the therapeutic potential of interrupting this pathway with IL-6 receptor blockade or by inhibiting its downstream effectors JAK1/2 or Stat3. These clinically relevant interventions did not inhibit tumor cell proliferation in vitro but had profound effects in vivo on tumor progression, interfering broadly with tumor-supportive stromal functions, including angiogenesis, fibroblast infiltration, and myeloid suppressor cell recruitment in both the tumor and pre-metastatic niche. This study provides the first evidence for IL-6 expression at the leading edge of invasive human breast tumors and demonstrates mechanistically that IL-6/JAK/Stat3 signaling plays a critical and pharmacologically targetable role in orchestrating the composition of the tumor microenvironment that promotes growth, invasion, and metastasis.

Published
2013

46. MAP kinase kinase 1 (MEK1) within extracellular vesicles inhibits tumour growth by promoting anti-tumour immunity.

Author

Searles SC, Chen WS, Yee JD, Lee P, Lee CK, Caron C, Neto F, Matei I, Lyden D, and Bui JD

Subjects
Animals, Mice, Macrophages immunology, Macrophages metabolism, Cell Line, Tumor, Mice, Inbred C57BL, Humans, Neoplasms immunology, Neoplasms therapy, Interferon-gamma metabolism, Interferon-gamma immunology, Adaptive Immunity, Female, Cell Proliferation, Extracellular Vesicles metabolism, Extracellular Vesicles immunology, MAP Kinase Kinase 1 metabolism
Abstract

Extracellular vesicles (EVs) mediate intercellular communication in many physiologic processes and can modulate immune responses in individuals with cancer. Most studies of EVs in cancer have focused on their tumour promoting properties. Whether and how EVs might mediate tumour regression besides carrying antigens has not been well characterized. Using a mouse model of highly immunogenic regressor versus poorly immunogenic progressor tumour cells, we have characterized the role of EVs in activating macrophages and promoting tumour rejection. We found that the signalling molecule MAP2K1 (MEK1) is enriched in EVs secreted by regressor relative to progressor cells. Progressor EVs engineered to have levels of MEK1 similar to regressor EVs could inhibit tumour growth by indirectly promoting adaptive immunity in both syngeneic and 3rd party tumours. This effect required MEK1 activity and could occur by activating macrophages to promote adaptive immune responses against the tumour via the cytokine interferon-gamma. Our results suggest that MEK inhibition may be deleterious to cancer treatment, since MEK1 plays an important cell-extrinsic, tumour-suppressive role within EVs. Moreover, the delivery of MEK1 to tumour-associated macrophages, either by EVs, nanoparticles, or some other means, could be a useful strategy to treat cancer via the activation of anti-tumour immunity., (© 2024 The Author(s). Journal of Extracellular Vesicles published by Wiley Periodicals LLC on behalf of International Society for Extracellular Vesicles.)

Published
2024
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47. Multi-parametric atlas of the pre-metastatic liver for prediction of metastatic outcome in early-stage pancreatic cancer.

Author

Bojmar L, Zambirinis CP, Hernandez JM, Chakraborty J, Shaashua L, Kim J, Johnson KE, Hanna S, Askan G, Burman J, Ravichandran H, Zheng J, Jolissaint JS, Srouji R, Song Y, Choubey A, Kim HS, Cioffi M, van Beek E, Sigel C, Jessurun J, Velasco Riestra P, Blomstrand H, Jönsson C, Jönsson A, Lauritzen P, Buehring W, Ararso Y, Hernandez D, Vinagolu-Baur JP, Friedman M, Glidden C, Firmenich L, Lieberman G, Mejia DL, Nasar N, Mutvei AP, Paul DM, Bram Y, Costa-Silva B, Basturk O, Boudreau N, Zhang H, Matei IR, Hoshino A, Kelsen D, Sagi I, Scherz A, Scherz-Shouval R, Yarden Y, Oren M, Egeblad M, Lewis JS, Keshari K, Grandgenett PM, Hollingsworth MA, Rajasekhar VK, Healey JH, Björnsson B, Simeone DM, Tuveson DA, Iacobuzio-Donahue CA, Bromberg J, Vincent CT, O'Reilly EM, DeMatteo RP, Balachandran VP, D'Angelica MI, Kingham TP, Allen PJ, Simpson AL, Elemento O, Sandström P, Schwartz RE, Jarnagin WR, and Lyden D

Subjects
Humans, Male, Female, Middle Aged, Aged, Biopsy, Neoplasm Staging, Pancreatectomy, Extracellular Traps metabolism, Prognosis, Pancreatic Neoplasms pathology, Pancreatic Neoplasms genetics, Pancreatic Neoplasms surgery, Liver Neoplasms secondary, Liver Neoplasms pathology, Liver Neoplasms genetics, Liver pathology, Liver metabolism
Abstract

Metastasis occurs frequently after resection of pancreatic cancer (PaC). In this study, we hypothesized that multi-parametric analysis of pre-metastatic liver biopsies would classify patients according to their metastatic risk, timing and organ site. Liver biopsies obtained during pancreatectomy from 49 patients with localized PaC and 19 control patients with non-cancerous pancreatic lesions were analyzed, combining metabolomic, tissue and single-cell transcriptomics and multiplex imaging approaches. Patients were followed prospectively (median 3 years) and classified into four recurrence groups; early (<6 months after resection) or late (>6 months after resection) liver metastasis (LiM); extrahepatic metastasis (EHM); and disease-free survivors (no evidence of disease (NED)). Overall, PaC livers exhibited signs of augmented inflammation compared to controls. Enrichment of neutrophil extracellular traps (NETs), Ki-67 upregulation and decreased liver creatine significantly distinguished those with future metastasis from NED. Patients with future LiM were characterized by scant T cell lobular infiltration, less steatosis and higher levels of citrullinated H3 compared to patients who developed EHM, who had overexpression of interferon target genes (MX1 and NR1D1) and an increase of CD11B + natural killer (NK) cells. Upregulation of sortilin-1 and prominent NETs, together with the lack of T cells and a reduction in CD11B + NK cells, differentiated patients with early-onset LiM from those with late-onset LiM. Liver profiles of NED closely resembled those of controls. Using the above parameters, a machine-learning-based model was developed that successfully predicted the metastatic outcome at the time of surgery with 78% accuracy. Therefore, multi-parametric profiling of liver biopsies at the time of PaC diagnosis may determine metastatic risk and organotropism and guide clinical stratification for optimal treatment selection., (© 2024. The Author(s), under exclusive licence to Springer Nature America, Inc.)

Published
2024
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48. Role of the afferent lymph as an immunological conduit to analyze tissue antigenic and inflammatory load.

Author

Nanaware PP, Khan ZN, Clement CC, Shetty M, Mota I, Seltzer ES, Dzieciatkowska M, Gamboni F, D'Alessandro A, Ng C, Nagayama M, Lichti CF, Soni RK, Jacob B Geri, Matei I, Lyden D, Longman R, Lu TT, Wan X, Unanue ER, Stern LJ, and Santambrogio L

Subjects
Animals, Mice, Humans, Male, Female, Inflammatory Bowel Diseases immunology, Inflammatory Bowel Diseases pathology, Inflammatory Bowel Diseases metabolism, Dendritic Cells immunology, Dendritic Cells metabolism, Lymph metabolism, Lymph immunology, Inflammation immunology, Inflammation pathology, Inflammation metabolism, Lymph Nodes immunology, Lymph Nodes metabolism, Mice, Inbred C57BL, Antigens metabolism, Antigens immunology
Abstract

The lymphatic fluid is the conduit by which part of the tissue "omics" is transported to the draining lymph node for immunosurveillance. Following cannulation of the pre-nodal cervical and mesenteric afferent lymphatics, herein we investigate the lymph proteomic composition, uncovering that its composition varies according to the tissue of origin. Tissue specificity is also reflected in the dendritic cell-major histocompatibility complex class II-eluted immunopeptidome harvested from the cervical and mesenteric nodes. Following inflammatory disruption of the gut barrier, the lymph antigenic and inflammatory loads are analyzed in both mice and subjects with inflammatory bowel diseases. Gastrointestinal tissue damage reflects the lymph inflammatory and damage-associated molecular pattern signatures, microbiome-derived by-products, and immunomodulatory molecules, including metabolites of the gut-brain axis, mapped in the afferent mesenteric lymph. Our data point to the relevance of the lymphatic fluid to probe the tissue-specific antigenic and inflammatory load transported to the draining lymph node for immunosurveillance., Competing Interests: Declaration of interests The authors declare that they do not have any conflict of interest., (Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)

Published
2024
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49. Collection of biospecimens from the inspiration4 mission establishes the standards for the space omics and medical atlas (SOMA).

Author

Overbey EG, Ryon K, Kim J, Tierney BT, Klotz R, Ortiz V, Mullane S, Schmidt JC, MacKay M, Damle N, Najjar D, Matei I, Patras L, Garcia Medina JS, Kleinman AS, Wain Hirschberg J, Proszynski J, Narayanan SA, Schmidt CM, Afshin EE, Innes L, Saldarriaga MM, Schmidt MA, Granstein RD, Shirah B, Yu M, Lyden D, Mateus J, and Mason CE

Subjects
Humans, Exobiology, Metagenomics standards, Specimen Handling standards, Space Flight, Biological Specimen Banks standards, Preservation, Biological standards
Abstract

The SpaceX Inspiration4 mission provided a unique opportunity to study the impact of spaceflight on the human body. Biospecimen samples were collected from four crew members longitudinally before (Launch: L-92, L-44, L-3 days), during (Flight Day: FD1, FD2, FD3), and after (Return: R + 1, R + 45, R + 82, R + 194 days) spaceflight, spanning a total of 289 days across 2021-2022. The collection process included venous whole blood, capillary dried blood spot cards, saliva, urine, stool, body swabs, capsule swabs, SpaceX Dragon capsule HEPA filter, and skin biopsies. Venous whole blood was further processed to obtain aliquots of serum, plasma, extracellular vesicles and particles, and peripheral blood mononuclear cells. In total, 2,911 sample aliquots were shipped to our central lab at Weill Cornell Medicine for downstream assays and biobanking. This paper provides an overview of the extensive biospecimen collection and highlights their processing procedures and long-term biobanking techniques, facilitating future molecular tests and evaluations.As such, this study details a robust framework for obtaining and preserving high-quality human, microbial, and environmental samples for aerospace medicine in the Space Omics and Medical Atlas (SOMA) initiative, which can aid future human spaceflight and space biology experiments., (© 2024. The Author(s).)

Published
2024
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50. Single-cell multi-ome and immune profiles of the Inspiration4 crew reveal conserved, cell-type, and sex-specific responses to spaceflight.

Author

Kim J, Tierney BT, Overbey EG, Dantas E, Fuentealba M, Park J, Narayanan SA, Wu F, Najjar D, Chin CR, Meydan C, Loy C, Mathyk B, Klotz R, Ortiz V, Nguyen K, Ryon KA, Damle N, Houerbi N, Patras LI, Schanzer N, Hutchinson GA, Foox J, Bhattacharya C, Mackay M, Afshin EE, Hirschberg JW, Kleinman AS, Schmidt JC, Schmidt CM, Schmidt MA, Beheshti A, Matei I, Lyden D, Mullane S, Asadi A, Lenz JS, Mzava O, Yu M, Ganesan S, De Vlaminck I, Melnick AM, Barisic D, Winer DA, Zwart SR, Crucian BE, Smith SM, Mateus J, Furman D, and Mason CE

Subjects
Animals, Female, Male, Humans, Mice, Astronauts, Cytokines metabolism, T-Lymphocytes immunology, Sex Factors, Gene Expression Profiling, Oxidative Phosphorylation, Space Flight, Single-Cell Analysis, Transcriptome
Abstract

Spaceflight induces an immune response in astronauts. To better characterize this effect, we generated single-cell, multi-ome, cell-free RNA (cfRNA), biochemical, and hematology data for the SpaceX Inspiration4 (I4) mission crew. We found that 18 cytokines/chemokines related to inflammation, aging, and muscle homeostasis changed after spaceflight. In I4 single-cell multi-omics data, we identified a "spaceflight signature" of gene expression characterized by enrichment in oxidative phosphorylation, UV response, immune function, and TCF21 pathways. We confirmed the presence of this signature in independent datasets, including the NASA Twins Study, the I4 skin spatial transcriptomics, and 817 NASA GeneLab mouse transcriptomes. Finally, we observed that (1) T cells showed an up-regulation of FOXP3, (2) MHC class I genes exhibited long-term suppression, and (3) infection-related immune pathways were associated with microbiome shifts. In summary, this study reveals conserved and distinct immune disruptions occurring and details a roadmap for potential countermeasures to preserve astronaut health., (© 2024. The Author(s).)

Published
2024
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