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1. Erdafitinib in patients with advanced solid tumours with FGFR alterations (RAGNAR): an international, single-arm, phase 2 study

Author

Pant, S, Schuler, M, Iyer, G, Witt, O, Doi, T, Qin, S, Tabernero, J, Reardon, D, Massard, C, Minchom, A, Lugowska, I, Carranza, O, Arnold, D, Gutierrez, M, Winter, H, Stuyckens, K, Crow, L, Najmi, S, Hammond, C, Thomas, S, Santiago-Walker, A, Triantos, S, Sweiti, H, Loriot, Y, Greco, M, Coward, J, Joshua, A, Karapetis, C, Hart, C, Zhang, A, Prenen, H, Goeminne, J, Machiels, J, Rottey, S, Corassa, M, Molin, G, Tiscoski, K, Jardim, D, Mak, M, Fu, W, Yao, H, Huang, J, Jiang, H, Chen, B, Yan, D, Yang, Y, Le Tourneau, C, Penel, N, Salas, S, Blay, J, Brachet, P, Durando, X, Emambux, S, Ravaud, A, Folprecht, G, Ahrens, M, Golf, A, Haag, G, Lordick, F, Desuki, A, Cazzaniga, M, Ciardiello, F, Milella, M, Koyama, T, Hirooka, Y, Okamoto, W, Aogi, K, Kuboki, Y, Lee, J, Kim, S, Ahn, M, Chang, J, Kim, Y, Nam, D, Park, J, Paz-Ares, L, Moreno, V, Cervantes, A, Calvo, M, Falcon, A, Gonzalez, A, Martinez Bueno, A, Garcia-Corbacho, J, Longo, F, Yen, C, Chen, J, Hou, M, Chao, Y, Rau, K, Chiu, T, Feng, Y, Hsu, C, Huang, W, Lai, K, Yeh, S, Palmer, D, Welsh, L, Plummer, R, Bilen, M, Arrowsmith, E, Spigel, D, Zandberg, D, Doroshow, D, Lu-Emerson, C, Moezi, M, Paulson, S, Ward, P, Chaves, J, Grigg, C, Hussein, A, Manda, S, Monticelli, M, Qamar, R, Richey, S, Tamura, D, Wilks, S, Pant S., Schuler M., Iyer G., Witt O., Doi T., Qin S., Tabernero J., Reardon D. A., Massard C., Minchom A., Lugowska I., Carranza O., Arnold D., Gutierrez M., Winter H., Stuyckens K., Crow L., Najmi S., Hammond C., Thomas S., Santiago-Walker A., Triantos S., Sweiti H., Loriot Y., Greco M. A., Coward J., Joshua A., Karapetis C., Hart C., Zhang A., Prenen H., Goeminne J. -C., Machiels J. -P., Rottey S., Corassa M., Molin G. Z. D., Tiscoski K., Jardim D. L. F., Mak M., Fu W., Yao H., Huang J., Jiang H., Chen B., Yan D., Yang Y., Le Tourneau C., Penel N., Salas S., Blay J. -Y., Brachet P. -E., Durando X., Emambux S., Ravaud A., Folprecht G., Ahrens M., Golf A., Haag G. M., Lordick F., Desuki A., Cazzaniga M., Ciardiello F., Milella M., Koyama T., Hirooka Y., Okamoto W., Aogi K., Kuboki Y., Lee J., Kim S. -B., Ahn M. -J., Chang J. H., Kim Y. -M., Nam D. -H., Park J. -S., Paz-Ares L., Moreno V., Cervantes A., Calvo M., Falcon A., Gonzalez A., Martinez Bueno A., Garcia-Corbacho J., Longo F., Yen C. -J., Chen J. -S., Hou M. -F., Chao Y., Rau K. -M., Chiu T. -J., Feng Y. -H., Hsu C. -H., Huang W. -T., Lai K. -M., Yeh S. -P., Palmer D., Welsh L., Plummer R., Bilen M., Arrowsmith E., Spigel D. R., Zandberg D. P., Doroshow D., Lu-Emerson C., Moezi M., Paulson S., Reardon D., Ward P., Chaves J., Grigg C., Hussein A., Manda S., Monticelli M., Qamar R., Richey S. L., Tamura D., Wilks S., Pant, S, Schuler, M, Iyer, G, Witt, O, Doi, T, Qin, S, Tabernero, J, Reardon, D, Massard, C, Minchom, A, Lugowska, I, Carranza, O, Arnold, D, Gutierrez, M, Winter, H, Stuyckens, K, Crow, L, Najmi, S, Hammond, C, Thomas, S, Santiago-Walker, A, Triantos, S, Sweiti, H, Loriot, Y, Greco, M, Coward, J, Joshua, A, Karapetis, C, Hart, C, Zhang, A, Prenen, H, Goeminne, J, Machiels, J, Rottey, S, Corassa, M, Molin, G, Tiscoski, K, Jardim, D, Mak, M, Fu, W, Yao, H, Huang, J, Jiang, H, Chen, B, Yan, D, Yang, Y, Le Tourneau, C, Penel, N, Salas, S, Blay, J, Brachet, P, Durando, X, Emambux, S, Ravaud, A, Folprecht, G, Ahrens, M, Golf, A, Haag, G, Lordick, F, Desuki, A, Cazzaniga, M, Ciardiello, F, Milella, M, Koyama, T, Hirooka, Y, Okamoto, W, Aogi, K, Kuboki, Y, Lee, J, Kim, S, Ahn, M, Chang, J, Kim, Y, Nam, D, Park, J, Paz-Ares, L, Moreno, V, Cervantes, A, Calvo, M, Falcon, A, Gonzalez, A, Martinez Bueno, A, Garcia-Corbacho, J, Longo, F, Yen, C, Chen, J, Hou, M, Chao, Y, Rau, K, Chiu, T, Feng, Y, Hsu, C, Huang, W, Lai, K, Yeh, S, Palmer, D, Welsh, L, Plummer, R, Bilen, M, Arrowsmith, E, Spigel, D, Zandberg, D, Doroshow, D, Lu-Emerson, C, Moezi, M, Paulson, S, Ward, P, Chaves, J, Grigg, C, Hussein, A, Manda, S, Monticelli, M, Qamar, R, Richey, S, Tamura, D, Wilks, S, Pant S., Schuler M., Iyer G., Witt O., Doi T., Qin S., Tabernero J., Reardon D. A., Massard C., Minchom A., Lugowska I., Carranza O., Arnold D., Gutierrez M., Winter H., Stuyckens K., Crow L., Najmi S., Hammond C., Thomas S., Santiago-Walker A., Triantos S., Sweiti H., Loriot Y., Greco M. A., Coward J., Joshua A., Karapetis C., Hart C., Zhang A., Prenen H., Goeminne J. -C., Machiels J. -P., Rottey S., Corassa M., Molin G. Z. D., Tiscoski K., Jardim D. L. F., Mak M., Fu W., Yao H., Huang J., Jiang H., Chen B., Yan D., Yang Y., Le Tourneau C., Penel N., Salas S., Blay J. -Y., Brachet P. -E., Durando X., Emambux S., Ravaud A., Folprecht G., Ahrens M., Golf A., Haag G. M., Lordick F., Desuki A., Cazzaniga M., Ciardiello F., Milella M., Koyama T., Hirooka Y., Okamoto W., Aogi K., Kuboki Y., Lee J., Kim S. -B., Ahn M. -J., Chang J. H., Kim Y. -M., Nam D. -H., Park J. -S., Paz-Ares L., Moreno V., Cervantes A., Calvo M., Falcon A., Gonzalez A., Martinez Bueno A., Garcia-Corbacho J., Longo F., Yen C. -J., Chen J. -S., Hou M. -F., Chao Y., Rau K. -M., Chiu T. -J., Feng Y. -H., Hsu C. -H., Huang W. -T., Lai K. -M., Yeh S. -P., Palmer D., Welsh L., Plummer R., Bilen M., Arrowsmith E., Spigel D. R., Zandberg D. P., Doroshow D., Lu-Emerson C., Moezi M., Paulson S., Reardon D., Ward P., Chaves J., Grigg C., Hussein A., Manda S., Monticelli M., Qamar R., Richey S. L., Tamura D., and Wilks S.

Abstract

Background: FGFR alterations are reported across various malignancies and might act as oncogenic drivers in multiple histologies. Erdafitinib is an oral, selective pan-FGFR tyrosine kinase inhibitor with activity in FGFR-altered advanced urothelial carcinoma. We aimed to evaluate the safety and activity of erdafitinib in previously treated patients with FGFR-altered advanced solid tumours. Methods: The single-arm, phase 2 RAGNAR study was conducted at 156 investigative centres (hospitals or oncology practices that are qualified oncology study centres) across 15 countries. The study consisted of four cohorts based on tumour histology and patient age; the results reported in this Article are for the primary cohort of the study, defined as the Broad Panel Cohort, which was histology-agnostic. We recruited patients aged 12 years or older with advanced or metastatic tumours of any histology (except urothelial cancer) with predefined FGFR1–4 alterations (mutations or fusions according to local or central testing). Eligible patients had disease progression on at least one previous line of systemic therapy and no alternative standard therapy available to them, and an Eastern Cooperative Oncology Group performance status of 0–1 (or equivalent for adolescents aged 12–17 years). Patients received once-daily oral erdafitinib (8 mg/day with provision for pharmacodynamically guided up-titration to 9 mg/day) on a continuous 21-day cycle until disease progression or intolerable toxicity. The primary endpoint was objective response rate by independent review committee according to Response Evaluation Criteria In Solid Tumors (RECIST), version 1.1, or Response Assessment In Neuro-Oncology (RANO). The primary analysis was conducted on the treated population of the Broad Panel Cohort. This ongoing study is registered with ClinicalTrials.gov, number NCT04083976. Findings: Patients were recruited between Dec 5, 2019, and Feb 15, 2022. Of 217 patients treated with erdafitinib, 97 (45%) pa

Published
2023

3. 451O Preliminary evidence of clinical activity from phase I and Ib trials of the CLK/DYRK inhibitor cirtuvivint (CIRT) in subjects with advanced solid tumors

Author

Scott, A., primary, Call, J.A., additional, Chandana, S., additional, Borazanci, E., additional, Falchook, G.S., additional, Bordoni, R., additional, Richey, S., additional, Starodub, A., additional, Chung, V., additional, Lakhani, N.J., additional, Lam, E., additional, Schaffer, K., additional, Wang, J.S., additional, Shapiro, G., additional, Sachdev, J.C., additional, Beaupre, D., additional, and Tolcher, A.W., additional

Published
2022
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7. Collateral Damage

Author

Richey, Sean

Subjects
Trump, Donald Trump, immigration, anti-immigration, rhetoric, anti-immigration rhetoric, immigration rhetoric, incorporation, political parties, Republican Party, American identity, patriotism, survey data, experiments, content analysis, second generation, second generation Americans, immigrants, linked fate, America, thema EDItEUR::J Society and Social Sciences::JB Society and culture: general, thema EDItEUR::J Society and Social Sciences::JB Society and culture: general::JBC Cultural and media studies::JBCT Media studies, thema EDItEUR::J Society and Social Sciences::JB Society and culture: general::JBS Social groups, communities and identities::JBSL Ethnic studies::JBSL1 Ethnic groups and multicultural studies, thema EDItEUR::J Society and Social Sciences::JP Politics and government
Abstract

Collateral Damage provides an overview of how political communication influences the process of incorporation with the broad society as well as its political parties. Sean Richey shows that how politicians talk about immigrants affects how their children perceive America and their feelings about the nation. These perceptions and feelings in turn greatly influence the children’s desire to incorporate into American political society. He also shows that regardless of a speaker’s intended outcome, what is said can still have a deleterious effect on incorporation desire, a communicative process that he terms “collateral damage.” Richey uses new experimental and survey evidence, as well as the rhetoric of Donald Trump as a test case, to examine how anti-immigration communication influences the incorporation of the children of immigrants.

Published
2023
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8. Preliminary safety and efficacy of rovalpituzumab tesirine in patients with delta-like protein 3-expressing advanced solid tumors

Author

Aggarwal, R., primary, Mansfield, A., additional, Beltran, H., additional, Farago, A.F., additional, Hann, C.L., additional, Kaye, F., additional, Lewis, K., additional, Niu, J., additional, Richey, S., additional, Smith, D., additional, Soares, H.P., additional, Spira, A., additional, Taylor, M., additional, Waqar, S.N., additional, Lally, S., additional, Rossi, M., additional, Saunders, L., additional, Dylla, S.J., additional, Kavalerchik, E., additional, and Anthony, L., additional

Published
2017
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9. P0125 A phase 1/2 trial of BNC105P with everolimus in metastatic renal cell carcinoma

Author

Pal, S., primary, Azad, A., additional, Bhatia, S., additional, Drabkin, H., additional, Costello, B., additional, Sarantopoulos, J., additional, Kanesvaran, R., additional, Lauer, R., additional, Sweeney, C., additional, Hahn, N., additional, Sonpavde, G., additional, Richey, S., additional, Breen, T., additional, Kremmidiotis, G., additional, Leske, A., additional, Doolin, E., additional, Bibby, D., additional, Simpson, J., additional, Iglesias, J., additional, and Hutson, T., additional

Published
2015
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11. A Phase I/II Trial of Bnc105P with Everolimus in Metastatic Renal Cell Carcinoma (Mrcc): Results of the Randomized Phase Ii Disruptor-1 Trial

Author

Pal, S., primary, Azad, A., additional, Bhatia, S., additional, Drabkin, H., additional, Costello, B., additional, Sarantopolous, J., additional, Kanesvaran, R., additional, Lauer, R., additional, Sweeney, C., additional, Hahn, N.M., additional, Sonpavde, G., additional, Richey, S., additional, Breen, T., additional, Kremmidiotis, G., additional, Doolin, E., additional, Bibby, D., additional, Simpson, J., additional, Iglesias, J., additional, and Hutson, T., additional

Published
2014
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12. Reconstruction of Family-Level Phylogenetic Relationships within Demospongiae (Porifera) Using Nuclear Encoded Housekeeping Genes

Author

Hill, M. S., Hill, A. L., Lopez, J., Peterson, K. J., Pomponi, S., Diaz, M. C., Thacker, R. W., Adamska, M., Boury-Esnault, N., Cárdenas, Paco, Chaves-Fonnegra, A., Danka, E., De Laine, B. -O, Formica, D., Hajdu, E., Lobo-Hajdu, G., Klontz, S., Morrow, C. C., Patel, J., Picton, B., Pisani, D., Pohlmann, D., Redmond, N. E., Reed, J., Richey, S., Riesgo, A., Rubin, E., Russell, Z., Rützler, K., Sperling, E. A., di Stefano, M., Tarver, J. E., Collins, A. G., Hill, M. S., Hill, A. L., Lopez, J., Peterson, K. J., Pomponi, S., Diaz, M. C., Thacker, R. W., Adamska, M., Boury-Esnault, N., Cárdenas, Paco, Chaves-Fonnegra, A., Danka, E., De Laine, B. -O, Formica, D., Hajdu, E., Lobo-Hajdu, G., Klontz, S., Morrow, C. C., Patel, J., Picton, B., Pisani, D., Pohlmann, D., Redmond, N. E., Reed, J., Richey, S., Riesgo, A., Rubin, E., Russell, Z., Rützler, K., Sperling, E. A., di Stefano, M., Tarver, J. E., and Collins, A. G.

Abstract

Background: Demosponges are challenging for phylogenetic systematics because of their plastic and relatively simple morphologies and many deep divergences between major clades. To improve understanding of the phylogenetic relationships within Demospongiae, we sequenced and analyzed seven nuclear housekeeping genes involved in a variety of cellular functions from a diverse group of sponges. Methodology/Principal Findings: We generated data from each of the four sponge classes (i.e., Calcarea, Demospongiae, Hexactinellida, and Homoscleromorpha), but focused on family-level relationships within demosponges. With data for 21 newly sampled families, our Maximum Likelihood and Bayesian-based approaches recovered previously phylogenetically defined taxa: Keratosap, Myxospongiaep, Spongillidap, Haploscleromorphap (the marine haplosclerids) and Democlaviap. We found conflicting results concerning the relationships of Keratosap and Myxospongiaep to the remaining demosponges, but our results strongly supported a clade of Haploscleromorphap+Spongillidap+Democlaviap. In contrast to hypotheses based on mitochondrial genome and ribosomal data, nuclear housekeeping gene data suggested that freshwater sponges (Spongillidap) are sister to Haploscleromorphap rather than part of Democlaviap. Within Keratosap, we found equivocal results as to the monophyly of Dictyoceratida. Within Myxospongiaep, Chondrosida and Verongida were monophyletic. A well-supported clade within Democlaviap, Tetractinellidap, composed of all sampled members of Astrophorina and Spirophorina (including the only lithistid in our analysis), was consistently revealed as the sister group to all other members of Democlaviap. Within Tetractinellidap, we did not recover monophyletic Astrophorina or Spirophorina. Our results also reaffirmed the monophyly of order Poecilosclerida (excluding Desmacellidae and Raspailiidae), and polyphyly of Hadromerida and Halichondrida. Conclusions/Significance: These results, using an ind

Published
2013
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27. The Veterans Aging Cohort Study: observational studies of alcohol use, abuse, and outcomes among human immunodeficiency virus-infected veterans.

Author

Conigliaro J, Madenwald T, Bryant K, Braithwaite S, Gordon A, Fultz SL, Maisto S, Samet J, Kraemer K, Cook R, Day N, Roach D, Richey S, and Justice A

Abstract

This article represents the proceedings of a symposium at the 2003 annual meeting of the Research Society on Alcoholism in Fort Lauderdale, FL. The organizers/chairs were Joseph Conigliaro and Amy Justice. The presentations were (1) Introduction, by Joseph Conigliaro and Tamra Madenwald; (2) Alcohol and HIV/AIDS: the importance of integrative and translational research, by Kendall Bryant; (3) Alcohol use and abuse among patients with HIV infection, by Joseph Conigliaro and Stephan Maisto; (4) Severity of comorbid alcohol use/abuse in HIV infection, by Amy Justice and Jeffrey Samet; (5) Estimating the impact of alcohol use on long-term HIV outcomes, by Scott Braithwaite and Amy Justice; (6) Homelessness, drug & alcohol use among HIV+ veterans, by Adam Gordon and Robert Cook; and (7) Hepatitis C & alcohol in the VACS 3 study, by Shawn Fultz and Kevin Kraemer. The symposium concluded with a discussion led and facilitated by Diedra Roach. [ABSTRACT FROM AUTHOR]

Published
2004
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30. Silver(I) Scorpionate Mediated Insertion of Carbenes into Aliphatic C−H Bonds

Author

Dias, H. V. R., Browning, R. G., Richey, S. A., and Lovely, C. J.

Abstract

Silver(I) adducts featuring highly fluorinated tris(pyrazolyl)borate, [HB(3,5-(CF3)2Pz)3]-, catalyze the carbene insertion into carbon−hydrogen bonds of cyclic and acyclic hydrocarbons at room temperature. These silver complexes are more effective than related copper catalysts such as [HB(3,5-(CF3)2Pz)3]Cu(THF) for hydrocarbon activation via this route.

Published
2004

31. Prostate cancer, version 1.2014: Featured updates to the NCCN Guidelines

Author

Mohler, J. L., Philip Kantoff, Armstrong, A. J., Bahnson, R. R., Cohen, M., D Amico, A. V., Eastham, J. A., Enke, C. A., Farrington, T. A., Higano, C. S., Horwitz, E. M., Kawachi, M. H., Kuettel, M., Lee, R. J., Macvicar, G. R., Malcolm, A. W., Miller, D., Plimack, E. R., Pow-Sang, J. M., Richey, S., Roach Iii, M., Rohren, E., Rosenfeld, S., Small, E. J., Srinivas, S., Stein, C., Strope, S. A., Tward, J., Walsh, P. C., Shead, D. A., and Ho, M.

32. Prostate Cancer,,Version 2.2014 Clinical Practice Guidelines in Oncology

Author

Mohler, J. L., Kantoff, P. W., Armstrong, A. J., Bahnson, R. R., Cohen, M., D Amico, A. V., Eastham, J. A., Enke, C. A., Farrington, T. A., Higano, C. S., Horwitz, E. M., Kane, C. J., Kawachi, M. H., Kuettel, M., Kuzel, T. M., Lee, R. J., Malcolm, A. W., Miller, D., Plimack, E. R., Pow-Sang, J. M., Raben, D., Richey, S., Roach Iii, M., Rohren, E., Rosenfeld, S., Schaeffer, E., Small, E. J., Sonpavde, G., Srinivas, S., Stein, C., Seth Strope, Tward, J., Shead, D. A., and Ho, M.

33. Kidney cancer: Clinical practice guidelines

Author

Motzer, R. J., Carducci, M. A., Fishman, M., Hancock, S. L., Hauke, R. J., Hudes, G. R., Philip Kantoff, Kuzel, T. M., Lange, P. H., Levine, E. G., Logothetis, C., Margolin, K. A., Pili, R., Pohar, K. S., Redman, B. G., Richey, S., Robertson, C. N., Samlowski, W. E., Sheinfeld, J., and Urban, D. A.

34. Testicular cancer: Clinical practice guidelines

Author

Motzer, R. J., Bahnson, R. R., Boston, B., Carducci, M. A., Fishman, M., Hancock, S. L., Hauke, R. J., Hudes, G. R., Kantoff, P., Kuzel, T. M., Lange, P. H., Levine, E. G., Logothetis, C., Kim Margolin, Redman, B. G., Richey, S., Robertson, C. N., Samlowski, W. E., Sheinfeld, J., and Urban, D. A.

35. Prostate cancer, version 1.2016: Featured updates to the NCCN guidelines

Author

Mohler, J. L., Armstrong, A. J., Bahnson, R. R., D Amico, A. V., Davis, B. J., Eastham, J. A., Enke, C. A., Farrington, T. A., Higano, C. S., Horwitz, E. M., Hurwitz, M., Kane, C. J., Kawachi, M. H., Kuettel, M., Lee, R. J., Meeks, J. J., Penson, D. F., Plimack, E. R., Pow-Sang, J. M., Raben, D., Richey, S., Roach, M., Rosenfeld, S., Schaeffer, E., Skolarus, T. A., Small, E. J., Sonpavde, G., Srinivas, S., Strope, S. A., Jonathan Tward, Shead, D. A., and Freedman-Cass, D. A.

37. Is it time to change Army culture?

Author

Richey, Stephen W., Maj, Ret

Subjects
ARMY - United States, MILITARY PLANNING - United States, SPECIAL OPERATIONS FORCES, OFFICERS - Army - United States, MILITARY ART AND SCIENCE
Abstract

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Published
2015

43. THE ETIOLOGY OF TINNITUS AURIUM.

Author

RICHEY, S. O.

Abstract

Impaired hearing and tinnitus aurium are the two most common and distressing subjective symptoms of affections of the ear for which our aid is sought. Often the individual has reconciled himself to the impaired hearing, but is urgent for relief from the persistent torturing sounds of which he has the monopoly. The character of the tinnitus exciting most complaint is the ringing, buzzing, twittering, ticking or grating sound, which is as constant as the chronic progressive deafness with which it is associated, varying only in power or intensity at different times.Of the many causes of tinnitus aurium a number are promptly recognized, and have only to be understood to be relieved, viz., small objects on the drum membrane, or in the external meatus; obstruction of the Eustachian tube, or of the external auditory meatus; overdoses of quinia or of the salicylates; the use of tobacco or alcohol in some

Published
1896
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44. TAXIS IN INCREASED INTRA-OCULAR TENSION.

Author

RICHEY, S. O.

Abstract

The principal arteries of the globe enter it posteriorly and pierce the sclerotic directly, limiting as far as possible resistance to the access of nutrient blood. On the other hand, the veins pass very obliquely through the sclerotic in channels varying from 1.5 mm. to 5.5 mm. in length and contain no valves distal to their junction with the ophthalmic vein. The intra-ocular vessels have no vaso-motor constrictors, and the tension of the eyeball depends upon the pressure in the extra-ocular arterial current1; after death it is lowered. Given an abnormal propulsive force in the extra-ocular arterial current from any cause, and the increased influx of arterial blood raises intra-ocular pressure. So long as this influx does not exceed the ability of the venous system to remove it, the increased tension is within the limits of safety; but should there be any slowing of the outflow of venous blood,

Published
1897
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46. Proteogenomic and metabolomic characterization of human glioblastoma

Author

Cristina E. Tognon, Larisa Polonskaya, Tara Skelly, Shuang Cai, Francesmary Modugno, Larissa Rossell, Nancy Roche, Chen Huang, Jessika Baral, Fulvio D'Angelo, Wen-Wei Liang, Chia-Feng Tsai, Sneha P. Couvillion, Karin D. Rodland, Jun Zhu, Liang-Bo Wang, Paul D. Piehowski, Antonio Colaprico, Anupriya Agarwal, Matthew A. Wyczalkowski, Umut Ozbek, Francesca Petralia, Alexis Demopoulos, William W. Maggio, Lin Chen, Katherine A. Hoadley, Richard D. Smith, Sandra Cottingham, John McGee, Marcin J. Domagalski, Houxiang Zhu, Emek Demir, Rebecca I. Montgomery, Jamie Moon, Rashna Madan, George D. Wilson, Luciano Garofano, Ewa P. Malc, Chelsea J. Newton, Steven A. Carr, Chandan Kumar-Sinha, Donghui Tan, Christopher R. Kinsinger, Oxana Paklina, Weiqing Wan, Stephanie De Young, Sandra Cerda, Shankha Satpathy, Wojciech Kaspera, Linda Hannick, Gad Getz, Runyu Hong, Shuangjia Lu, Ziad Hanhan, Daniel C. Rohrer, Annette Marrero-Oliveras, Wojciech Szopa, Yuxing Liao, Amanda G. Paulovich, Jiayi Ji, Denis A. Golbin, Tara Hiltke, Weiva Sieh, Piotr A. Mieczkowski, Matthew E. Monroe, Gilbert S. Omenn, Jill S. Barnholtz-Sloan, Azra Krek, Bing Zhang, Brittany Henderson, Peter B. McGarvey, Ratna R. Thangudu, Maciej Wiznerowicz, Saravana M. Dhanasekaran, Alex Webster, Kai Li, Karna Robinson, Nan Ji, Karl K. Weitz, Simina M. Boca, Xiaoyu Song, Anna Calinawan, Adam C. Resnick, Brian J. Druker, Dana R. Valley, David J. Clark, Tao Liu, Eric J. Jaehnig, Alicia Francis, Michele Ceccarelli, Rui Zhao, Dmitry Rykunov, Boris Reva, Elizabeth R. Duffy, Antonio Iavarone, Dave Tabor, Joshua F. McMichael, Daniel Cui Zhou, Maureen Dyer, Kimberly Elburn, Scott D. Jewell, Negin Vatanian, Shirley Tsang, Seungyeul Yoo, Alexander R. Pico, Grace Zhao, Kent J. Bloodsworth, Chet Birger, Jena Lilly, Eunkyung An, Jeffrey R. Whiteaker, Albert H. Kim, Yige Wu, Karen A. Ketchum, Felipe D. Leprevost, Alcida Karz, Uma Borate, Nathan Edwards, Uma Velvulou, Melissa Borucki, Vasileios Stathias, Sanford P. Markey, Corbin D. Jones, Ronald J. Moore, MacIntosh Cornwell, Karsten Krug, Michael J. Birrer, James Suh, Tomasz Czernicki, Jason E. McDermott, Emily S. Boja, Pei Wang, Nina Martinez, Wenke Liu, Yan Shi, Lili Blumenberg, Emily Kawaler, Jeffrey W. Tyner, Feng Chen, Jakub Stawicki, Ki Sung Um, Arul M. Chinnaiyan, Robert Zelt, Jacob J. Day, Zhen Zhang, Caleb M. Lindgren, Li Ding, Nikolay Gabrovski, Hongwei Liu, Jonathan T. Lei, Alla Karpova, Ramani B. Kothadia, Sailaja Mareedu, Mitual Amin, Hannah Boekweg, Jennifer E. Kyle, Sara R. Savage, Brian R. Rood, Yuriy Zakhartsev, Matthew L. Anderson, Alyssa Charamut, Wagma Caravan, Shakti Ramkissoon, Junmei Wang, Song Cao, Samuel H. Payne, Rosalie K. Chu, Rajiv Dhir, David W. Andrews, Galen Hostetter, Liqun Qi, Zhiao Shi, Milan G. Chheda, Robert Edwards, Hui Zhang, Weiping Ma, Jennifer M. 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Subjects
Proteomics, 0301 basic medicine, Cancer Research, CPTAC, Histone H2B acetylation, Protein Tyrosine Phosphatase, Non-Receptor Type 11, Computational biology, Biology, Article, 03 medical and health sciences, lipidome, 0302 clinical medicine, Metabolomics, proteogenomic, Humans, Phosphorylation, EP300, proteomic, Proteogenomics, acetylome, single nuclei RNA-seq, Brain Neoplasms, Phospholipase C gamma, glioblastoma, Computational Biology, Lipidome, 030104 developmental biology, Histone, Oncology, Acetylation, 030220 oncology & carcinogenesis, Mutation, biology.protein, metabolome, signaling
Abstract

Glioblastoma (GBM) is the most aggressive nervous system cancer. Understanding its molecular pathogenesis is crucial to improving diagnosis and treatment. Integrated analysis of genomic, proteomic, post-translational modification and metabolomic data on 99 treatment-naive GBMs provides insights to GBM biology. We identify key phosphorylation events (e.g., phosphorylated PTPN11 and PLCG1) as potential switches mediating oncogenic pathway activation, as well as potential targets for EGFR-, TP53-, and RB1-altered tumors. Immune subtypes with distinct immune cell types are discovered using bulk omics methodologies, validated by snRNA-seq, and correlated with specific expression and histone acetylation patterns. Histone H2B acetylation in classical-like and immune-low GBM is driven largely by BRDs, CREBBP, and EP300. Integrated metabolomic and proteomic data identify specific lipid distributions across subtypes and distinct global metabolic changes in IDH-mutated tumors. This work highlights biological relationships that could contribute to stratification of GBM patients for more effective treatment. Wang et al. perform integrated proteogenomic analysis of adult glioblastoma (GBM), including metabolomics, lipidomics, and single nuclei RNA-Seq, revealing insights into the immune landscape of GBM, cell-specific nature of EMT signatures, histone acetylation in classical GBM, and the existence of signaling hubs which could provide therapeutic vulnerabilities.

Published
2021

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