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1. A T cell receptor targeting a recurrent driver mutation in FLT3 mediates elimination of primary human acute myeloid leukemia in vivo

Author

Giannakopoulou, Eirini, Lehander, Madeleine, Virding Culleton, Stina, Yang, Weiwen, Li, Yingqian, Karpanen, Terhi, Yoshizato, Tetsuichi, Rustad, Even H., Nielsen, Morten Milek, Bollineni, Ravi Chand, Tran, Trung T., Delic-Sarac, Marina, Gjerdingen, Thea Johanne, Douvlataniotis, Karolos, Laos, Maarja, Ali, Muhammad, Hillen, Amy, Mazzi, Stefania, Chin, Desmond Wai Loon, Mehta, Adi, Holm, Jeppe Sejerø, Bentzen, Amalie Kai, Bill, Marie, Griffioen, Marieke, Gedde-Dahl, Tobias, Lehmann, Sören, Jacobsen, Sten Eirik W., Woll, Petter S., and Olweus, Johanna

Published
2023
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2. Author Correction: Titers of antibodies against ancestral SARS-CoV-2 correlate with levels of neutralizing antibodies to multiple variants

Author

Tran, Trung The, Vaage, Eline Benno, Mehta, Adi, Chopra, Adity, Tietze, Lisa, Kolderup, Anette, Anthi, Aina, König, Marton, Nygaard, Gro, Lind, Andreas, Müller, Fredrik, Nissen-Meyer, Lise Sofie, Magnus, Per, Trogstad, Lill, Mjaaland, Siri, Søraas, Arne, Midtvedt, Karsten, Åsberg, Anders, Barratt-Due, Andreas, Medhus, Asle W., Høivik, Marte Lie, Lundin, Knut, Karlsen, Randi Fuglaas, Dahle, Reidun, Danielsson, Karin, Thomassen, Kristine Stien, Kro, Grete Birkeland, Cox, Rebecca J., Zhou, Fan, Langeland, Nina, Aukrust, Pål, Melum, Espen, Åvitsland, Tone Lise, Wiencke, Kristine, Holter, Jan Cato, Munthe, Ludvig A., Grødeland, Gunnveig, Andersen, Jan-Terje, Vaage, John Torgils, and Lund-Johansen, Fridtjof

Published
2023
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3. Titers of antibodies against ancestral SARS-CoV-2 correlate with levels of neutralizing antibodies to multiple variants

Author

Tran, Trung The, Vaage, Eline Benno, Mehta, Adi, Chopra, Adity, Tietze, Lisa, Kolderup, Anette, Anthi, Aina, König, Marton, Nygaard, Gro, Lind, Andreas, Müller, Fredrik, Nissen-Meyer, Lise Sofie, Magnus, Per, Trogstad, Lill, Mjaaland, Siri, Søraas, Arne, Midtvedt, Karsten, Åsberg, Anders, Barratt-Due, Andreas, Medhus, Asle W., Høivk, Marte Lie, Lundin, Knut, Karlsen, Randi Fuglaas, Dahle, Reidun, Danielsson, Karin, Thomassen, Kristine Stien, Kro, Grete Birkeland, Cox, Rebecca J., Zhou, Fan, Langeland, Nina, Aukrust, Pål, Melum, Espen, Åvitsland, Tone Lise, Wiencke, Kristine, Holter, Jan Cato, Munthe, Ludvig A., Grødeland, Gunnveig, Andersen, Jan-Terje, Vaage, John Torgils, and Lund-Johansen, Fridtjof

Published
2022
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4. Type I Interferon Autoantibodies Correlate With Cellular Immune Alterations in Severe COVID-19.

Author

Strunz, Benedikt, Maucourant, Christopher, Mehta, Adi, Wan, Hui, Du, Likun, Sun, Dan, Chen, Puran, Nordlander, Anna, Gao, Yu, Cornillet, Martin, Bister, Jonna, Kvedaraite, Egle, Christ, Wanda, Klingström, Jonas, Geanon, Daniel, Parke, Åsa, Ekwall-Larson, Anna, Rivino, Laura, MacAry, Paul A, and Aleman, Soo

Subjects
COVID-19, COVID-19 pandemic, TYPE I interferons, BACTERIAL diseases, VIRUS diseases
Abstract

Background Infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) can lead to severe disease with increased morbidity and mortality among certain risk groups. The presence of autoantibodies against type I interferons (aIFN-Abs) is one mechanism that contributes to severe coronavirus disease 2019 (COVID-19). Methods This study aimed to investigate the presence of aIFN-Abs in relation to the soluble proteome, circulating immune cell numbers, and cellular phenotypes, as well as development of adaptive immunity. Results aIFN-Abs were more prevalent in critical compared to severe COVID-19 but largely absent in the other viral and bacterial infections studied here. The antibody and T-cell response to SARS-CoV-2 remained largely unaffected by the presence aIFN-Abs. Similarly, the inflammatory response in COVID-19 was comparable in individuals with and without aIFN-Abs. Instead, presence of aIFN-Abs had an impact on cellular immune system composition and skewing of cellular immune pathways. Conclusions Our data suggest that aIFN-Abs do not significantly influence development of adaptive immunity but covary with alterations in immune cell numbers. [ABSTRACT FROM AUTHOR]

Published
2024
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5. Spatial-proteomics reveals phospho-signaling dynamics at subcellular resolution

Author

Martinez-Val, Ana, Bekker-Jensen, Dorte B., Steigerwald, Sophia, Koenig, Claire, Østergaard, Ole, Mehta, Adi, Tran, Trung, Sikorski, Krzysztof, Torres-Vega, Estefanía, Kwasniewicz, Ewa, Brynjólfsdóttir, Sólveig Hlín, Frankel, Lisa B., Kjøbsted, Rasmus, Krogh, Nicolai, Lundby, Alicia, Bekker-Jensen, Simon, Lund-Johansen, Fridtjof, and Olsen, Jesper V.

Published
2021
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7. 17-AAG and sihsp90α combinational therapy as a novel anti-cancer approach

Author

Mehta, Adi Behram

Subjects
610, RC0254 Neoplasms. Tumors. Oncology (including Cancer)
Abstract

Heat Shock Protein 90 (Hsp90) is a molecular chaperone which plays an active role in maintaining protein homeostasis. Hsp90 is known to be highly expressed in tumour cells where it regulates stability and function of several key oncogenic client proteins including Akt kinase, EGFR, CDK and PDGFR. These client proteins are mutated or overexpressed in tumours and are involved in tumour progression and metastasis due to their roles in signalling pathways, cell cycle and apoptosis. Hsp90 has two isoforms, namely Hsp90α and Hsp90β and share 85% sequence homology. Hsp90β is the constitutive isoform, however, Hsp90α is highly induced in many cancers and is responsible for tumourigenesis. Previous studies from our laboratory established Hsp90α mRNA and protein to be highly expressed in glioma cell lines and tissues compared to normal tissue and cells. In a follow up study, Hsp90α was silenced using predesigned small interfering RNA (sihsp90α) with high target specificity and it showed a clinical impact on the chemosensitivity to Temozolomide (TMZ). Thus, Hsp90α could be a therapeutic target for the treatment of glioma. This study utilized a Hsp90-inhibitor 17-AAG and hsp90α-specific siRNA (sihsp90α), either as single agent or in combination, to inhibit Hsp90 function in glioblastoma. Hsp90α mRNA and protein expression levels post treatment were evaluated using qRT-PCR and confocal microscopy. To determine if Hsp90α inhibition influenced Akt kinase activity, a Hsp90 client protein, Akt activity was examined in treated and control cells using a Akt Kinase activity kit. Novel results from the study revealed that Hsp90α was significantly down-regulated at both the mRNA and protein levels which were associated with reduced cell viability. Hsp90α inhibition resulted in loss of Akt kinase activity which validated the role of Hsp90α in chaperoning tumour progression. The use of 17-AAG concomitant with sihsp90α did not demonstrate synergistic anti-tumour effects in glioblastoma in vitro. Furthermore, the application of siRNA as an alternative to small-molecule inhibitors in the treatment of human disease has shown therapeutic potential. However, a major hurdle to its utility has been the difficulty in delivering these anionic macromolecules in vivo. In this study, the ability of Tat peptide to enhance siRNA-mediated knockdown of hsp90α and siRNA stability in serum was investigated. In glioblastoma, Tat-mediated sihsp90α transfection concomitant with 17-AAG exhibited significant downregulation of Hsp90α mRNA and protein levels with increased peptide concentrations. Hsp90α suppression was associated with reduced Akt kinase activity and cell viability. The sihsp90α/Tat complex significantly improved sihsp90α stability in human serum for up to 36 h post serum exposure. Finally, the combination therapy induced hsp90α knockdown and reduced Akt kinase activity in vivo. Although these results are preliminary and requires further validation, the anti-cancer activity is promising. These results suggest that the combination treatment with sihsp90α and 17-AAG may have therapeutic potential in GBM.

Published
2012

10. Target organ expression and biomarker characterization of chemokine CCL21 in systemic sclerosis associated pulmonary arterial hypertension

Author

Didriksen, Henriette, primary, Molberg, Øyvind, additional, Mehta, Adi, additional, Jordan, Suzana, additional, Palchevskiy, Vyacheslav, additional, Fretheim, Håvard, additional, Gude, Einar, additional, Ueland, Thor, additional, Brunborg, Cathrine, additional, Garen, Torhild, additional, Midtvedt, Øyvind, additional, Andreassen, Arne K., additional, Lund-Johansen, Fridtjof, additional, Distler, Oliver, additional, Belperio, John, additional, and Hoffmann-Vold, Anna-Maria, additional

Published
2022
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11. Titers of antibodies the receptor-binding domain (RBD) of ancestral SARS-CoV-2 are predictive for levels of neutralizing antibodies to multiple variants

Author

Lund-Johansen, Fridtjof, primary, Tran, Trung, additional, Vaage, Eline, additional, Mehta, Adi, additional, Chopra, Adity, additional, Kolderup, Anette, additional, Anthi, Aina, additional, König, Marton, additional, Nygaard, Gro, additional, Lind, Andreas, additional, Müller, Fredrik, additional, Nissen-Meyer, Lise, additional, Magnus, Per, additional, Trogstad, Lill-Iren Schou, additional, Mjaaland, Siri, additional, Søraas, Arne, additional, Midtvedt, Karsten, additional, Åsberg, Anders, additional, Barratt-Due, Andreas, additional, Medhus, Asle Wilhelm, additional, Høivik, Marte Lie, additional, Lundin, Knut E. A., additional, Karlsen, Randi, additional, Dahle, Reidun, additional, Danielsson, Karin, additional, Thomassen, Kristine, additional, Kro, Grete Birkeland, additional, Cox, Rebecca, additional, Zhou, Fan, additional, Langeland, Nina, additional, Aukrust, Pål, additional, Melum, Espen, additional, Åvitsland, Tone, additional, Wiencke, Kristine, additional, Holter, Jan, additional, Munthe, Ludvig, additional, Grodeland, Gunnveig, additional, Andersen, Jan, additional, and Vaage, John, additional

Published
2022
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12. Target organ expression and biomarker characterization of chemokine CCL21 in systemic sclerosis associated pulmonary arterial hypertension

Author

Didriksen, Henriette; https://orcid.org/0000-0003-1600-5271, Molberg, Øyvind, Mehta, Adi, Jordan, Suzana; https://orcid.org/0000-0002-8114-8239, Palchevskiy, Vyacheslav, Fretheim, Håvard, Gude, Einar, Ueland, Thor, Brunborg, Cathrine, Garen, Torhild, Midtvedt, Øyvind, Andreassen, Arne K, Lund-Johansen, Fridtjof; https://orcid.org/0000-0002-2445-1258, Distler, Oliver; https://orcid.org/0000-0002-0546-8310, Belperio, John, Hoffmann-Vold, Anna-Maria; https://orcid.org/0000-0001-6467-7422, Didriksen, Henriette; https://orcid.org/0000-0003-1600-5271, Molberg, Øyvind, Mehta, Adi, Jordan, Suzana; https://orcid.org/0000-0002-8114-8239, Palchevskiy, Vyacheslav, Fretheim, Håvard, Gude, Einar, Ueland, Thor, Brunborg, Cathrine, Garen, Torhild, Midtvedt, Øyvind, Andreassen, Arne K, Lund-Johansen, Fridtjof; https://orcid.org/0000-0002-2445-1258, Distler, Oliver; https://orcid.org/0000-0002-0546-8310, Belperio, John, and Hoffmann-Vold, Anna-Maria; https://orcid.org/0000-0001-6467-7422

Abstract

Introduction: Systemic sclerosis (SSc) is a heterogenous disorder that appears to result from interplay between vascular pathologies, tissue fibrosis and immune processes, with evidence for deregulation of chemokines, which normally control immune trafficking. We recently identified altered levels of chemokine CCL21 in SSc associated pulmonary arterial hypertension (PAH). Here, we aimed to define target organ expression and biomarker characteristics of CCL21. Materials and methods: To investigate target organ expression of CCL21, we performed immunohistochemistry (IHC) on explanted lung tissues from SSc-PAH patients. We assessed serum levels of CCL21 by ELISA and Luminex in two well-characterized SSc cohorts from Oslo (OUH, n=552) and Zurich (n=93) University hospitals and in 168 healthy controls. For detection of anti-CCl21 antibodies, we performed protein array analysis applying serum samples from SSc patients (n=300) and healthy controls. To characterize circulating CCL21 in SSc, we applied immunoprecipitation (IP) with antibodies detecting both full length and tailless and a custom-made antibody detecting only the C-terminal of CCL21. IP products were analyzed by SDS-PAGE/western blot and Mass spectrometry (MS). Results: By IHC, we found that CCL21 was mainly expressed in the airway epithelial cells of SSc patients with PAH. In the analysis of serum levels of CCL21 we found weak correlation between Luminex and ELISA (r=0.515, p<0.001). Serum levels of anti-CCL21 antibodies were higher in SSc patients than in healthy controls (p<0.001), but only 5% of the SSc population were positive for anti-CCL21 antibodies in SSc, and we found no correlation between anti-CCl21 and serum levels of CCL21. By MS, we only identified peptides located within amino acid (aa) 23-102 of CCL21, indicating that CCL21 in SSc circulate as a truncated protein without the C-terminal tail. Conclusion: This study demonstrates expression of CCL21 in epithelial lung tissue from SSc patients with

Published
2022

13. Multiplexed measurement of binding- and neutralizing antibodies to SARS-CoV-2 variants in 12.000 post-vaccine sera

Author

Tran, Trung, primary, Vaage, Eline, additional, Mehta, Adi, additional, Chopra, Adity, additional, Kolderup, Anette, additional, Anthi, Aina, additional, König, Marton, additional, Nygard, Gro, additional, Lind, Andreas, additional, Muller, Fredrik, additional, Nissen-Meyer, Lise-Sofie, additional, Magnus, Per, additional, Trogstad, Lill-Iren, additional, Mjaaland, Siri, additional, Søraas, Arne, additional, Midtvedt, Karsten, additional, Åsberg, Anders, additional, Barratt-Due, Andreas, additional, Medhus, Asle, additional, Høivik, Marte, additional, Lundin, Knut, additional, Karlsen, Randi, additional, Dahle, Reidun, additional, Danielsson, Karin, additional, Thomassen, Kristine, additional, Kro, Grete, additional, Cox, Rebecca, additional, Zhou, Fan, additional, Langeland, Nina, additional, Aukrust, Pal, additional, Holter, Jan, additional, Melum, Espen, additional, Åvitsland, Tone, additional, Wiencke, Kristine, additional, Munthe, Ludvig, additional, Grodeland, Gunnveig, additional, Andersen, Jan Terje, additional, Vaage, John, additional, and Lund-Johansen, Fridtjof, additional

Published
2022
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14. Spatial-proteomics reveal in-vivo phospho-signaling dynamics at subcellular resolution

Author

Martinez Del Val, Ana, Bekker-Jensen, Dorte B, Steigerwald, Sophia, Mehta, Adi, Tran, Trung, Sikorski, Krzysztof, Torres Vega, Estefania, Kwasniewicz, Ewa, Brynjólfsdóttir, Sólveig Hlín, Frankel, Lisa, Kjøbsted, Rasmus, Krogh, Nicolai, Lundby, Alicia, Bekker-Jensen, Simon, Lund-Johansen, Fridtjof, Olsen, Jesper Velgaard, Martinez Del Val, Ana, Bekker-Jensen, Dorte B, Steigerwald, Sophia, Mehta, Adi, Tran, Trung, Sikorski, Krzysztof, Torres Vega, Estefania, Kwasniewicz, Ewa, Brynjólfsdóttir, Sólveig Hlín, Frankel, Lisa, Kjøbsted, Rasmus, Krogh, Nicolai, Lundby, Alicia, Bekker-Jensen, Simon, Lund-Johansen, Fridtjof, and Olsen, Jesper Velgaard

Abstract

Dynamic change in subcellular localization of signaling proteins is a general concept that eukaryotic cells evolved for eliciting a coordinated response to stimuli. Mass spectrometry (MS)-based proteomics in combination with subcellular fractionation can provide comprehensive maps of spatio-temporal regulation of cells, but involves laborious workflows that does not cover the phospho-proteome level. Here we present a high-throughput workflow based on sequential cell fractionation to profile the global proteome and phospho-proteome dynamics across six distinct subcellular fractions. We benchmarked the workflow by studying spatio-temporal EGFR phospho-signaling dynamics in-vitro in HeLa cells and in-vivo in mouse tissues. Finally, we investigated the spatio-temporal stress signaling, revealing cellular relocation of ribosomal proteins in response to hypertonicity and muscle contraction. Proteomics data generated in this study can be explored through https://SpatialProteoDynamics.github.io.

Published
2021

16. Spatial-proteomics reveal in-vivo phospho-signaling dynamics at subcellular resolution

Author

Martinez-Val, Ana, primary, Bekker-Jensen, Dorte B., additional, Steigerwald, Sophia, additional, Mehta, Adi, additional, Tran, Trung, additional, Sikorski, Krzysztof, additional, Torres-Vega, Estefanía, additional, Kwasniewicz, Ewa, additional, Brynjólfsdóttir, Sólveig Hlín, additional, Frankel, Lisa B., additional, Kjøbsted, Rasmus, additional, Krogh, Nicolai, additional, Lundby, Alicia, additional, Bekker-Jensen, Simon, additional, Lund-Johansen, Fridtjof, additional, and Olsen, Jesper V., additional

Published
2021
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18. Contributors

Author

Abdelmalak, Joseph B., primary, Abelson, Abby, additional, Absi, Ahmed, additional, Achkar, Edgar, additional, Adelstein, David J., additional, Adhami, Talal, additional, Adury, Kamal, additional, Advani, Anjali, additional, Al-Ashkar, Feyrouz, additional, AlMahameed, Amjad, additional, Amado, Antoine, additional, Armogida, Sheila, additional, Armstrong, Wendy S., additional, Arroliga, Mercedes E., additional, Arroliga, Alejandro C., additional, Ashton, Kathleen, additional, Askari, Arman, additional, Atanaskova, Natasha, additional, Attaran, Marjan, additional, Aucejo, Federico, additional, Austerman, Joseph, additional, Avery, Robin, additional, Aydin, H. Nail, additional, Barnes, David, additional, Bartholomew, John R., additional, Batur, Pelin, additional, Baz, Rachid, additional, Bergfeld, Wilma, additional, Bhatt, Deepak, additional, Bharadwaj, Swati, additional, Bianchi, Laura K., additional, Boike, Allan, additional, Bolooki, Michael H., additional, Bolwell, Brian, additional, Bott-Silverman, Corinne, additional, Boyle, Andrew, additional, Bradley, Linda, additional, Braun, William E., additional, Braver, Yvonne, additional, Brener, Sorin J., additional, Brethauer, Stacy, additional, Budev, Marie M., additional, Bunyard, Matthew, additional, Burke, Carol, additional, Butt, Saud, additional, Calabrese, Leonard, additional, Camisa, Charles, additional, Caldwell, Darwin L., additional, Carey, John, additional, Carey, William D., additional, Cesario, Karin, additional, Cevasco, Nathaniel, additional, Chapman, Jeffrey T., additional, Chatterjee, Soumya, additional, Chen, Michael C., additional, Cherian, Neil, additional, Chinnappa, Priya, additional, Choure, Anuja, additional, Chung, Jeffrey Y., additional, Collins, Gregory B., additional, Covington, Edward C., additional, Culver, Daniel A., additional, Curtin, Ronan, additional, Davis, Mellar, additional, Deitcher, Steven, additional, Demirjian, Sevag, additional, Dreicer, Robert, additional, Dresing, Thomas J., additional, Dweik, Raed A., additional, Eghtesad, Bijan, additional, Elder, Julie A., additional, Embi, Peter J., additional, Englund, Kristin, additional, Erzurum, Serpil, additional, Factora, Ronan, additional, Fairbanks, Kyrsten, additional, Faith-Fernandez, Esteban, additional, Falcone, Tatiana, additional, Falcone, Tommaso, additional, Falk, Gary W., additional, Fanning, Suzanne R., additional, Fatica, Richard, additional, Fattal, Omar, additional, Faulx, Michael, additional, File, Elizabeth, additional, Fleseriu, Maria, additional, Fouad-Tarazi, Fetnat, additional, Fowler, Adele, additional, Fox, Robert, additional, Franco, Kathleen N., additional, Fraser, Thomas G., additional, Freda, Benjamin J., additional, Freeman, Katherine, additional, Fung, John J., additional, Garcia, Jorge, additional, Gildea, Thomas R., additional, Golish, Joseph A., additional, Gopinath, Anil, additional, Gordon, Steven, additional, Grandinetti, Lisa, additional, Grasso, Adam, additional, Griffin, Brian, additional, Grimm, Richard, additional, Hajj-Ali, Rula A., additional, Hall, Philip, additional, Hamrahian, Amir H., additional, Harrison, Shannon, additional, Hermida, Teresa, additional, Hernández-Rodriguez, José, additional, Heyka, Robert, additional, Hoffman, Gary S., additional, Hobbs, Robert, additional, Hong, Sandra, additional, Hoogwerf, Byron, additional, Hsieh, Fred, additional, Huang, Julie, additional, Husni, M. Elaine, additional, Ioachimescu, Adriana G., additional, Ioachimescu, Octavian C., additional, Isaacson, Harry J., additional, Isada, Carlos M., additional, Issa, Naim, additional, Jaber, Wael A., additional, Jacob, Ron, additional, Jaeger, Fredrick J., additional, Jaeger, Fred, additional, Jin, Xian Wen, additional, Juvelekian, Georges, additional, Kashyap, Sangeeta, additional, Katzan, Irene, additional, Kaur, Gurjit, additional, Kavuru, Mani, additional, Keys, Thomas F., additional, Khalife, Sami, additional, Khalil, Mazen K., additional, Khasnis, Atul, additional, Kim, Esther S.H., additional, Kim, Richard, additional, Kim, Alice, additional, Koelsch, R., additional, Koening, Curry L., additional, Kooken, Ann R., additional, Kothari, Shakuntala, additional, Krasuski, Richard A., additional, Kunkel, Robert, additional, Lakin, Milton, additional, Lang, David M., additional, LaRosa, Steven P., additional, Lascano, Martin E., additional, Lashner, Bret, additional, Leung, Anthony K., additional, Lever, Harry, additional, Lever, David S., additional, Levin, Kerry H., additional, Lichtin, Alan, additional, Lifshitz, Oren H., additional, Lim, Li Ling, additional, Logan, Daniel, additional, Lucas, Jennifer, additional, Magrey, Marina, additional, Maier, Michael, additional, Malone, Donald, additional, Manzon, Judith, additional, Maroo, Anjli, additional, Mathews, Manu, additional, Mawhorter, Steven D., additional, Mayer, Mark, additional, Mayuga, Ken, additional, Mazzone, Peter J., additional, McAllister, Mark S., additional, McCarthy, Kevin, additional, Maksimowicz-McKinnonn, Kathleen, additional, Mehta, Adi, additional, Mehta, Atul C., additional, Mekhail, Tarek, additional, Miller, Charles M., additional, Moffa, Donald, additional, Moheet, Asma, additional, Molloy, Eamonn, additional, Moore, Halle, additional, Morledge, Thomas, additional, Mossad, Sherif B., additional, Muthusamy, Preetha, additional, Muzina, David J., additional, Nair, Dileep, additional, Nally, Joseph, additional, Nasr, Christian, additional, Noeller, Thomas P., additional, Novaro, Gian M., additional, Nurko, Saul, additional, O'Shea, Robert S., additional, Padmanabhan, Ravindran, additional, Paschall, Velma L., additional, Pien, Lily C., additional, Piliang, Melissa, additional, Pimental, Ronnie, additional, Poggio, Emilio D., additional, Potts, Jeannette M., additional, Pozuelo, Leo, additional, Procop, Gary W., additional, Qadeer, Mohammed, additional, Radojicic, Christine, additional, Rafey, Mohammed, additional, Ranes, Justin L., additional, Raymond, Russell, additional, Remzi, Feza, additional, Rice, Thomas, additional, Rodriguez, Cristina, additional, Rowney, Jess, additional, Sabella, Camille, additional, Sabecks, Ronald M., additional, Sachdeva, Mandi, additional, Foldvary-Schaefer, Nancy, additional, Schauer, Philip, additional, Scheetz, Raymond, additional, Schmitt, Steven, additional, Schrieber, Martin, additional, Seballos, Raul J., additional, Schweikert, Robert A., additional, Sekeres, Mikkael A., additional, Shen, Bo, additional, Shields, Jr., Robert W., additional, Shivadas, Anita, additional, Shoemaker, Laura, additional, Shrestha, Nabin K., additional, Shrestha, Rabin K., additional, Silver, Bernard J., additional, Singh, Rishi P., additional, Singh, Vivek, additional, Skugor, Mario, additional, Smith, Stephen, additional, Soffer, Edy, additional, Solaiman, Firas Al, additional, Sood, Apra, additional, Stephany, Brian R., additional, Stevens, Tyler, additional, Stevens, Glen H.J., additional, Stoller, James K., additional, Streem, David, additional, Sweeney, Patrick, additional, Swiencicki, James F., additional, Taege, Alan, additional, Taliercio, Rachel M., additional, Tallman, Thomas, additional, Tavee, Jinny, additional, Tavill, Anthony, additional, Taylor, David, additional, Taylor, James S., additional, Tesar, George E., additional, Thacker, Holly L., additional, Theil, Karl, additional, Thornton, Sharon Longshore, additional, Tomecki, Kenneth J., additional, Tomford, Walton J., additional, Tung, Rebecca, additional, Tungsiripat, Marisa, additional, Vidimos, Allison, additional, Vogel, Nicola M., additional, Wakim-Fleming, Jamile, additional, Boon Wee, Teo, additional, Whinney, Christopher, additional, Wieckowska, Anna, additional, Wiedemann, Herbert P., additional, Wilke, William, additional, Woodhouse, Justin G., additional, Wright, Bridget, additional, Yamani, Mohamad, additional, Zanotti, Kristine, additional, Zein, Claudia O., additional, Zimmerman, Robert, additional, and Zirwas, Matthew J., additional

Published
2010
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20. 443 An immunotherapy trio in advanced HNSCC for coordinated B and T cell antigen response

Author

Fox, Bernard, primary, Moudgil, Tarsem, additional, Hilton, Traci, additional, Iwamoto, Noriko, additional, Paustian, Christopher, additional, Mehta, Adi, additional, Lund-Johansen, Fridtjof, additional, Sanborn, Rachel, additional, Bell, Bryan, additional, Laws, Madeleine, additional, McDonnell, Glenna, additional, Koguchi, Yoshinobu, additional, Bifulco, Carlo, additional, Piening, Brian, additional, Merino, Carmen Ballesteros, additional, Jensen, Shawn, additional, Shimada, Takashi, additional, Hu, Hong-Ming, additional, Urba, Walter, additional, Leidner, Rom, additional, and Couey, Marcus, additional

Published
2020
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31. T cell population expansion in response to allogeneic cancer vaccine alone (DPV-001) or with granulocyte-macrophage colony-stimulating factor (GM-CSF) or imiquimod (I) for definitively-treated stage III NSCLC patients (pts).

Author

Fox, Bernard A., primary, Boulmay, Brian C., additional, Li, Rui, additional, Happel, Kyle T, additional, Paustian, Christopher, additional, Moudgil, Tarsem Lal, additional, Puri, Sachin, additional, Dubay, Christopher, additional, Koguchi, Yoshinobu, additional, Mehta, Adi, additional, Lund-Johansen, Fridtjof, additional, Fisher, Brenda K, additional, Redmond, William L, additional, Bifulco, Carlo Bruno, additional, Ochoa, Augusto, additional, Hu, Hong-Ming, additional, Hilton, Traci, additional, Urba, Walter John, additional, and Sanborn, Rachel E., additional

Published
2017
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33. 31st Annual Meeting and Associated Programs of the Society for Immunotherapy of Cancer (SITC 2016): late breaking abstracts

Author

Althammer, Sonja, primary, Steele, Keith, additional, Rebelatto, Marlon, additional, Tan, Tze Heng, additional, Wiestler, Tobias, additional, Schmidt, Guenter, additional, Higgs, Brandon, additional, Li, Xia, additional, Shi, Li, additional, Jin, Xiaoping, additional, Antal, Joyce, additional, Gupta, Ashok, additional, Ranade, Koustubh, additional, Binning, Gerd, additional, Bellmunt, Joaquim, additional, de Wit, Ronald, additional, Vaughn, David J., additional, Fradet, Yves, additional, Lee, Jae Lyun, additional, Fong, Lawrence, additional, Vogelzang, Nicholas J., additional, Climent, Miguel A., additional, Petrylak, Daniel P., additional, Choueiri, Toni K., additional, Necchi, Andrea, additional, Gerritsen, Winald, additional, Gurney, Howard, additional, Quinn, David I., additional, Culine, Stéphane, additional, Sternberg, Cora N., additional, Mai, Yabing, additional, Puhlmann, Markus, additional, Perini, Rodolfo F., additional, Bajorin, Dean F., additional, Sharma, Padmanee, additional, Callahan, Margaret K., additional, Calvo, Emiliano, additional, Kim, Joseph W., additional, de Braud, Filipo, additional, Ott, Patrick A., additional, Bono, Petri, additional, Pillai, Rathi N., additional, Morse, Michael, additional, Le, Dung T., additional, Taylor, Matthew, additional, Spilliopoulou, Pavlina, additional, Bendell, Johanna, additional, Jaeger, Dirk, additional, Chan, Emily, additional, Antonia, Scott J., additional, Ascierto, Paolo A., additional, Hennicken, Delphine, additional, Tschaika, Marina, additional, Azrilevich, Alex, additional, Rosenberg, Jonathan, additional, Levy, Ofer, additional, Chan, Christopher, additional, Cojocaru, Gady, additional, Liang, Spencer, additional, Ophir, Eran, additional, Ganguly, Sudipto, additional, Toporik, Amir, additional, Kotturi, Maya, additional, Kfir, Tal Fridman, additional, Murter, Benjamin M., additional, Logronio, Kathryn, additional, Dassa, Liat, additional, Leung, Ling, additional, Greenwald, Shirley, additional, Azulay, Meir, additional, Kumar, Sandeep, additional, Alteber, Zoya, additional, Pan, Xiaoyu, additional, Machlenkin, Arthur, additional, Benita, Yair, additional, Drake, Andrew W., additional, Chajut, Ayelet, additional, Salomon, Ran, additional, Vankin, Ilan, additional, Safyon, Einav, additional, Hunter, John, additional, Levine, Zurit, additional, White, Mark, additional, Leidner, Rom, additional, Kang, Hyunseok, additional, Haddad, Robert, additional, Segal, Neil H., additional, Wirth, Lori J., additional, Ferris, Robert L., additional, Hodi, F. Stephen, additional, Sanborn, Rachel E., additional, Gajewski, Thomas F., additional, Sharfman, William, additional, McDonald, Dan, additional, Srivastava, Shivani, additional, Gu, Xuemin, additional, Phillips, Penny, additional, Passey, Chaitali, additional, Seiwert, Tanguy, additional, Habtetsion, Tsadik, additional, Zhou, Gang, additional, Sakellariou-Thompson, Donastas, additional, Haymaker, Cara, additional, Creasy, Caitlin, additional, Hurd, Mark, additional, Uraoka, Naohiro, additional, Canales, Jaime Rodriguez, additional, Koptez, Scott, additional, Hwu, Patrick, additional, Maitra, Anirban, additional, Bernatchez, Chantale, additional, Coyle, Scott M., additional, Roybel, Kole T., additional, Rupp, Levi J., additional, Santoro, Stephen P., additional, Secrest, Stephanie, additional, Spelman, Michael, additional, Ho, Hanson, additional, Gomes, Tina, additional, Tse, Tiffany, additional, Yung-Wu, Chia, additional, Taunton, Jack, additional, Lim, Wendell, additional, Emtage, Peter, additional, Moudgil, Tarsem, additional, Ballesteros-Merino, Carmen, additional, Hilton, Traci, additional, Paustian, Christopher, additional, Page, David, additional, Urba, Walter, additional, Fox, Bernard, additional, Bell, Bryan, additional, Patel, Ashish, additional, Olafsen, Tove, additional, Satpayev, Daulet, additional, Torgov, Michael, additional, Marchioni, Filippo, additional, Romero, Jason, additional, Jiang, Ziyue Karen, additional, Zamilpa, Charles, additional, Keppler, Jennifer S., additional, Mascioni, Alessandro, additional, Jia, Fang, additional, Lee, Chen-Yu, additional, Gudas, Jean, additional, Sullivan, Ryan J., additional, Hoshida, Yujin, additional, Logan, Theodore, additional, Khushalani, Nikhil, additional, Giobbie-Hurder, Anita, additional, Margolin, Kim, additional, Roder, Joanna, additional, Bhatt, Rupal, additional, Koon, Henry, additional, Olencki, Thomas, additional, Hutson, Thomas, additional, Curti, Brendan, additional, Blackmon, Shauna, additional, Mier, James W., additional, Puzanov, Igor, additional, Roder, Heinrich, additional, Stewart, John, additional, Amin, Asim, additional, Ernstoff, Marc S., additional, Clark, Joseph I., additional, Atkins, Michael B., additional, Kaufman, Howard L., additional, Sosman, Jeffrey, additional, Signoretti, Sabina, additional, McDermott, David F., additional, Anderson, Abraham A., additional, Milhem, Mohammed M., additional, Andtbacka, Robert H. I., additional, Minor, David, additional, Gorski, Kevin S., additional, Baker, Daniel M., additional, Hamid, Omid, additional, Akporiaye, Emmanuel, additional, Koguchi, Yoshinobu, additional, Sutcliffe, Kim, additional, Conder, Kristie, additional, Marron, Thomas, additional, Bhardwaj, Nina, additional, Hammerich, Linda, additional, George, Fiby, additional, Kim-Schulze, Seunghee, additional, Keler, Tibor, additional, Davis, Tom, additional, Crowley, Elizabeth, additional, Salazar, Andres, additional, Brody, Joshua, additional, Monjazeb, Arta, additional, Daly, Megan E., additional, Riess, Jonathan, additional, Li, Tianhong, additional, Murphy, William J., additional, Kelly, Karen, additional, Hu, Zhiwei, additional, Shen, Rulong, additional, Campbell, Amanda, additional, McMichael, Elizabeth, additional, Yu, Lianbo, additional, Ramaswam, Bhuvaneswari, additional, London, Cheryl A., additional, Xu, Tian, additional, Carson, William, additional, Kokolus, Kathleen M., additional, Repasky, Elizabeth A., additional, Schell, Todd D., additional, Drabick, Joseph D., additional, Messenheimer, David J., additional, Jensen, Shawn, additional, Rubinstein, Mark, additional, Andrijauskaite, Kristina, additional, Swiderska-syn, Marzena, additional, Lind, Kristin, additional, Choppin, Agnes, additional, Roell, Marina K., additional, Wrangle, John, additional, Rhode, Peter, additional, Wong, Hing, additional, Ahmad, Shamim, additional, Webb, Mason, additional, Abu-Eid, Rasha, additional, Shrimali, Rajeev, additional, Verma, Vivek, additional, Doroodchi, Atbin, additional, Berrong, Zuzana, additional, Yashar, David, additional, Samara, Raed, additional, Mkrtichyan, Mikayel, additional, Khleif, Samir, additional, Powell, Steven, additional, Gitau, Mark, additional, Sumey, Christopher, additional, Terrell, Andrew, additional, Lohr, Michele, additional, Nowak, Ryan K., additional, McGraw, Steven, additional, Jensen, Ash, additional, Blanchard, Miran, additional, Gold, Kathryn A., additional, Cohen, Ezra E. W., additional, Ellison, Christie, additional, Black, Lora, additional, Lee, John, additional, Spanos, William Chad, additional, Wennerberg, Erik, additional, Schwitzer, Emily, additional, Lhuillier, Claire, additional, Koelwyn, Graeme, additional, Hiner, Rebecca, additional, Jones, Lee, additional, Demaria, Sandra, additional, Amanda, Vandeveer, additional, Greiner, John W., additional, Schlom, Jeffrey, additional, Bookstaver, Michelle, additional, Jewell, Christopher M., additional, Gunderson, Andrew, additional, Boulmay, Brian, additional, Li, Rui, additional, Spieler, Bradley, additional, Happel, Kyle, additional, Feng, Zipei, additional, Dubay, Christopher, additional, Fisher, Brenda, additional, Aung, Sandra, additional, Mederos, Eileen, additional, Bifulco, Carlo B., additional, McNamara, Michael, additional, Bahjat, Keith, additional, Redmond, William, additional, Ochoa, Augusto, additional, Hu, Hong-Ming, additional, Mehta, Adi, additional, Lund-Johansen, Fridtjof, additional, Bedu-Addo, Frank, additional, Conn, Greg, additional, King, Michael, additional, Dutta, Panna, additional, Shepard, Robert, additional, Einstein, Mark, additional, Adams, Sylvia, additional, Wang, Ena, additional, Jin, Ping, additional, Novik, Yelena, additional, Morrison, Debra, additional, Oratz, Ruth, additional, Marincola, Franco M., additional, Stroncek, David, additional, Goldberg, Judith, additional, Formenti, Silvia C., additional, Galon, Jérôme, additional, Mlecnik, Bernhard, additional, Marliot, Florence, additional, Ou, Fang-Shu, additional, Lugli, Alessandro, additional, Zlobec, Inti, additional, Rau, Tilman T., additional, Nagtegaal, Iris D., additional, Vink-Borger, Elisa, additional, Hartmann, Arndt, additional, Geppert, Carol, additional, Roehrl, Michael H., additional, Bavi, Prashant, additional, Ohashi, Pamela S., additional, Wang, Julia Y., additional, Nguyen, Linh T., additional, Han, SeongJun, additional, MacGregor, Heather L., additional, Hafezi-Bakhtiari, Sara, additional, Wouters, Bradley G., additional, Kawakami, Yutaka, additional, Papivanova, Boryana, additional, Xu, Mingli, additional, Fujita, Tomonobu, additional, Hazama, Shoichi, additional, Suzuki, Nobuaki, additional, Nagano, Hiroaki, additional, Okuno, Kiyotaka, additional, Itoh, Kyogo, additional, Zavadova, Eva, additional, Vocka, Michal, additional, Spacek, Jan, additional, Petruzelka, Lubos, additional, Konopasek, Bohuslav, additional, Dundr, Pavel, additional, Skalova, Helena, additional, Torigoe, Toshihiko, additional, Sato, Noriyuki, additional, Furuhata, Tomohisa, additional, Takemasa, Ichiro, additional, Van den Eynde, Marc, additional, Jouret-Mourin, Anne, additional, Machiels, Jean-Pascal, additional, Fredriksen, Tessa, additional, Lafontaine, Lucie, additional, Buttard, Bénédicte, additional, Church, Sarah, additional, Maby, Pauline, additional, Angell, Helen, additional, Angelova, Mihaela, additional, Vasaturo, Angela, additional, Bindea, Gabriela, additional, Berger, Anne, additional, Lagorce, Christine, additional, Patel, Prabhu S., additional, Vora, Hemangini H., additional, Shah, Birva, additional, Patel, Jayendrakumar B., additional, Rajvik, Kruti N., additional, Pandya, Shashank J., additional, Shukla, Shilin N., additional, Wang, Yili, additional, Zhang, Guanjun, additional, Masucci, Giuseppe V., additional, Andersson, Emilia K., additional, Grizzi, Fabio, additional, Laghi, Luigi, additional, Botti, Gerardo, additional, Tatangelo, Fabiana, additional, Delrio, Paolo, additional, Cilberto, Gennaro, additional, Marincola, Franco, additional, Sargent, Daniel J., additional, Fox, Bernard A., additional, Algazi, Alain, additional, Tsai, Katy, additional, Rosenblum, Michael, additional, Nandoskar, Prachi, additional, Li, Amy, additional, Nonomura, John, additional, Takamura, Kathryn, additional, Dwyer, Mary, additional, Browning, Erica, additional, Talia, Reneta, additional, Twitty, Chris, additional, Gargosky, Sharron, additional, Campbell, Jean, additional, Le, Mai, additional, Pierce, Robert H., additional, Daud, Adil, additional, Gartrell, Robyn, additional, Marks, Douglas, additional, Stack, Edward, additional, Lu, Yan, additional, Izaki, Daisuke, additional, Beck, Kristen, additional, Jia, Dan Tong, additional, Armenta, Paul, additional, White-Stern, Ashley, additional, Fu, Yichun, additional, Blake, Zoe, additional, Taback, Bret, additional, Horst, Basil, additional, Saenger, Yvonne M., additional, Leonardo, Steven, additional, Gorden, Keith, additional, Fulton, Ross B., additional, Fraser, Kathryn, additional, Kangas, Takashi O., additional, Walsh, Richard, additional, Ertelt, Kathleen, additional, Graff, Jeremy, additional, Uhlik, Mark, additional, Sims, Jennifer S., additional, Lei, Liang, additional, Tsujiuchi, Takashi, additional, Bruce, Jeffrey N., additional, Canoll, Peter, additional, Tolcher, Anthony W, additional, Alley, Evan W, additional, Chichili, Gurunadh, additional, Canoll, Jan E, additional, Moore, Paul, additional, Bonvini, Ezio, additional, Johnson, Syd, additional, Shankar, Sadhna, additional, Vasselli, James, additional, Wigginton, Jon, additional, and Powderly, John, additional

Published
2016
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34. MetaMass, a tool for meta-analysis of subcellular proteomics data

Author

Lund-Johansen, Fridtjof, primary, de la Rosa Carrillo, Daniel, additional, Mehta, Adi, additional, Sikorski, Krzysztof, additional, Inngjerdingen, Marit, additional, Kalina, Tomas, additional, Røysland, Kjetil, additional, de Souza, Gustavo Antonio, additional, Bradbury, Andrew R M, additional, Lecrevisse, Quentin, additional, and Stuchly, Jan, additional

Published
2016
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36. A Novel Therapeutic Strategy for the Treatment of Glioma, Combining Chemical and Molecular Targeting of Hsp90a

Author

Mehta, Adi, Shervington, Leroy Alexander, Munje, Chinmay, Shervington, Amal A, Mehta, Adi, Shervington, Leroy Alexander, Munje, Chinmay, and Shervington, Amal A

Abstract

Hsp90α's vital role in tumour survival and progression, together with its highly inducible expression profile in gliomas and its absence in normal tissue and cell lines validates it as a therapeutic target for glioma. Hsp90α was downregulated using the post-transcriptional RNAi strategy (sihsp90α) and a post-translational inhibitor, the benzoquinone antibiotic 17-AAG. Glioblastoma U87-MG and normal human astrocyte SVGp12 were treated with sihsp90α, 17-AAG and concurrent sihsp90α/17-AAG (combined treatment). Both Hsp90α gene silencing and the protein inhibitor approaches resulted in a dramatic reduction in cell viability. Results showed that sihsp90α, 17-AAG and a combination of sihsp90α/17-AAG, reduced cell viability by 27%, 75% and 88% (p < 0.001), respectively, after 72 h. hsp90α mRNA copy numbers were downregulated by 65%, 90% and 99% after 72 h treatment with sihsp90α, 17-AAG and sihsp90α/17-AAG, respectively. The relationship between Hsp90α protein expression and its client Akt kinase activity levels were monitored following treatment with sihsp90α, 17-AAG and sihsp90α/17-AAG. Akt kinase activity was downregulated as a direct consequence of Hsp90α inhibition. Both Hsp90α and Akt kinase levels were significantly downregulated after 72 h. Although, 17-AAG when used as a single agent reduces the Hsp90α protein and the Akt kinase levels, the efficacy demonstrated by combinatorial treatment was found to be far more effective. Combination treatment reduced the Hsp90α protein and Akt kinase levels to 4.3% and 43%, respectively, after 72 h. hsp90α mRNA expression detected in SVGp12 was negligible compared to U87-MG, also, the combination treatment did not compromise the normal cell viability. Taking into account the role of Hsp90α in tumour progression and the involvement of Akt kinase in cell signalling and the anti-apoptotic pathways in tumours, this double targets treatment infers a novel therapeutic strategy.

Published
2011

38. A window to the future 2050.

Author

Mehta, Adi

Subjects
LIFE insurance, REINSURANCE, PROPERTY insurance, FINANCIAL planning
Published
2021

45. Efficacy and Safety of Inhaled Insulin (Exubera)Compared With Subcutaneous Insulin Therapy in PatientsWith Type 2 Diabetes.

Author

Hollander, Priscilla A., Blonde, Lawrence, Rowe, Richard, Mehta, Adi E., Milburn, Joseph L., Hershon, Kenneth S., Chiasson, Jean-Louis, and Levin, Seymour R.

Subjects
INSULIN therapy, HYPOGLYCEMIC agents, INJECTIONS, HYPOGLYCEMIA, DRUG administration, TREATMENT of diabetes
Abstract

OBJECTIVE -- Glycemic control using inhaled, dry-powder insulin plus a single injection of long-acting insulin was compared with a conventional regimen in patients with type 2 diabetes, which was previously managed with at least two daily insulin injections. RESEARCH DESIGN AND METHODS -- Patients were randomized to 6 months' treatment with either premeal inhaled insulin plus a bedtime dose of Ultralente (n = 149) or at least two daily injections of subcutaneous insulin (mixed regular/NPH insulin; n = 150). The primary efficacy end point was the change in HbA[sub1c] from baseline to the end of study. RESULTS -- HbA[sub1c] decreased similarly in the inhaled (-0.7%) and subcutaneous (-0.6%) insulin groups (adjusted treatment group difference: -0.07%, 95% CI -0.32 to 0.17). HbA[sub1c] <7.0% was achieved in more patients receiving inhaled (46.9%) than subcutaneous (31.7%) insulin (odds ratio 2.27, 95% CI 1.24-4.14). Overall hypoglycemia (events per subject-month) was slightly lower in the inhaled (1.4 events) than in the subcutaneous (1.6 events) insulin group (risk ratio 0.89, 95% CI 0.82-0.97), with no difference in severe events. Other adverse events, with the exception of increased cough in the inhaled insulin group, were similar. No difference in pulmonary function testing was seen. Further studies are underway to assess tolerability in the longer term. Insulin antibody binding increased more in the inhaled insulin group. Treatment satisfaction was greater in the inhaled insulin group. CONCLUSIONS -- Inhaled insulin appears to be effective, well tolerated, and well accepted in patients with type 2 diabetes and provides glycemic control comparable to a conventional subcutaneous regimen. [ABSTRACT FROM AUTHOR]

Published
2004
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47. 17-AAG and sihsp90α combinational therapy as a novel anti-cancer approach

Author

Mehta, Adi Behram

Subjects
A990
Abstract

Heat Shock Protein 90 (Hsp90) is a molecular chaperone which plays an active role in maintaining protein homeostasis. Hsp90 is known to be highly expressed in tumour cells where it regulates stability and function of several key oncogenic client proteins including Akt kinase, EGFR, CDK and PDGFR. These client proteins are mutated or overexpressed in tumours and are involved in tumour progression and metastasis due to their roles in signalling pathways, cell cycle and apoptosis. \ud \ud Hsp90 has two isoforms, namely Hsp90α and Hsp90β and share 85% sequence homology. Hsp90β is the constitutive isoform, however, Hsp90α is highly induced in many cancers and is responsible for tumourigenesis. Previous studies from our laboratory established Hsp90α mRNA and protein to be highly expressed in glioma cell lines and tissues compared to normal tissue and cells. In a follow up study, Hsp90α was silenced using predesigned small interfering RNA (sihsp90α) with high target specificity and it showed a clinical impact on the chemosensitivity to Temozolomide (TMZ). Thus, Hsp90α could be a therapeutic target for the treatment of glioma. \ud \ud This study utilized a Hsp90-inhibitor 17-AAG and hsp90α-specific siRNA (sihsp90α), either as single agent or in combination, to inhibit Hsp90 function in glioblastoma. Hsp90α mRNA and protein expression levels post treatment were evaluated using qRT-PCR and confocal microscopy. To determine if Hsp90α inhibition influenced Akt kinase activity, a Hsp90 client protein, Akt activity was examined in treated and control cells using a Akt Kinase activity kit. Novel results from the study revealed that Hsp90α was significantly down-regulated at both the mRNA and protein levels which were associated with reduced cell viability. Hsp90α inhibition resulted in loss of Akt kinase activity which validated the role of Hsp90α in chaperoning tumour progression. The use of 17-AAG concomitant with sihsp90α did not demonstrate synergistic anti-tumour effects in glioblastoma in vitro. \ud \ud Furthermore, the application of siRNA as an alternative to small-molecule inhibitors in the treatment of human disease has shown therapeutic potential. However, a major hurdle to its utility has been the difficulty in delivering these anionic macromolecules in vivo. In this study, the ability of Tat peptide to enhance siRNA-mediated knockdown of hsp90α and siRNA stability in serum was investigated. In glioblastoma, Tat-mediated sihsp90α transfection concomitant with 17-AAG exhibited significant downregulation of Hsp90α mRNA and protein levels with increased peptide concentrations. Hsp90α suppression was associated with reduced Akt kinase activity and cell viability. The sihsp90α/Tat complex significantly improved sihsp90α stability in human serum for up to 36 h post serum exposure. \ud \ud Finally, the combination therapy induced hsp90α knockdown and reduced Akt kinase activity in vivo. Although these results are preliminary and requires further validation, the anti-cancer activity is promising. These results suggest that the combination treatment with sihsp90α and 17-AAG may have therapeutic potential in GBM.

48. 31st Annual Meeting and Associated Programs of the Society for Immunotherapy of Cancer (SITC 2016): late breaking abstracts

Author

Althammer, Sonja, Steele, Keith, Rebelatto, Marlon, Tan, Tze Heng, Wiestler, Tobias, Schmidt, Guenter, Higgs, Brandon, Li, Xia, Shi, Li, Jin, Xiaoping, Antal, Joyce, Gupta, Ashok, Ranade, Koustubh, Binning, Gerd, Bellmunt, Joaquim, de Wit, Ronald, Vaughn, David J., Fradet, Yves, Lee, Jae Lyun, Fong, Lawrence, Vogelzang, Nicholas J., Climent, Miguel A., Petrylak, Daniel P., Choueiri, Toni K., Necchi, Andrea, Gerritsen, Winald, Gurney, Howard, Quinn, David I., Culine, Stéphane, Sternberg, Cora N., Mai, Yabing, Puhlmann, Markus, Perini, Rodolfo F., Bajorin, Dean F., Sharma, Padmanee, Callahan, Margaret K., Calvo, Emiliano, Kim, Joseph W., de Braud, Filipo, Ott, Patrick A., Bono, Petri, Pillai, Rathi N., Morse, Michael, Le, Dung T., Taylor, Matthew, Spilliopoulou, Pavlina, Bendell, Johanna, Jaeger, Dirk, Chan, Emily, Antonia, Scott J., Ascierto, Paolo A., Hennicken, Delphine, Tschaika, Marina, Azrilevich, Alex, Rosenberg, Jonathan, Levy, Ofer, Chan, Christopher, Cojocaru, Gady, Liang, Spencer, Ophir, Eran, Ganguly, Sudipto, Toporik, Amir, Kotturi, Maya, Kfir, Tal Fridman, Murter, Benjamin M., Logronio, Kathryn, Dassa, Liat, Leung, Ling, Greenwald, Shirley, Azulay, Meir, Kumar, Sandeep, Alteber, Zoya, Pan, Xiaoyu, Machlenkin, Arthur, Benita, Yair, Drake, Andrew W., Chajut, Ayelet, Salomon, Ran, Vankin, Ilan, Safyon, Einav, Hunter, John, Levine, Zurit, White, Mark, Leidner, Rom, Kang, Hyunseok, Haddad, Robert, Segal, Neil H., Wirth, Lori J., Ferris, Robert L., Hodi, F. Stephen, Sanborn, Rachel E., Gajewski, Thomas F., Sharfman, William, McDonald, Dan, Srivastava, Shivani, Gu, Xuemin, Phillips, Penny, Passey, Chaitali, Seiwert, Tanguy, Habtetsion, Tsadik, Zhou, Gang, Sakellariou-Thompson, Donastas, Haymaker, Cara, Creasy, Caitlin, Hurd, Mark, Uraoka, Naohiro, Canales, Jaime Rodriguez, Koptez, Scott, Hwu, Patrick, Maitra, Anirban, Bernatchez, Chantale, Coyle, Scott M., Roybel, Kole T., Rupp, Levi J., Santoro, Stephen P., Secrest, Stephanie, Spelman, Michael, Ho, Hanson, Gomes, Tina, Tse, Tiffany, Yung-Wu, Chia, Taunton, Jack, Lim, Wendell, Emtage, Peter, Moudgil, Tarsem, Ballesteros-Merino, Carmen, Hilton, Traci, Paustian, Christopher, Page, David, Urba, Walter, Fox, Bernard, Bell, Bryan, Patel, Ashish, Olafsen, Tove, Satpayev, Daulet, Torgov, Michael, Marchioni, Filippo, Romero, Jason, Jiang, Ziyue Karen, Zamilpa, Charles, Keppler, Jennifer S., Mascioni, Alessandro, Jia, Fang, Lee, Chen-Yu, Gudas, Jean, Sullivan, Ryan J., Hoshida, Yujin, Logan, Theodore, Khushalani, Nikhil, Giobbie-Hurder, Anita, Margolin, Kim, Roder, Joanna, Bhatt, Rupal, Koon, Henry, Olencki, Thomas, Hutson, Thomas, Curti, Brendan, Blackmon, Shauna, Mier, James W., Puzanov, Igor, Roder, Heinrich, Stewart, John, Amin, Asim, Ernstoff, Marc S., Clark, Joseph I., Atkins, Michael B., Kaufman, Howard L., Sosman, Jeffrey, Signoretti, Sabina, McDermott, David F., Anderson, Abraham A., Milhem, Mohammed M., Andtbacka, Robert H. I., Minor, David, Gorski, Kevin S., Baker, Daniel M., Hamid, Omid, Akporiaye, Emmanuel, Koguchi, Yoshinobu, Sutcliffe, Kim, Conder, Kristie, Marron, Thomas, Bhardwaj, Nina, Hammerich, Linda, George, Fiby, Kim-Schulze, Seunghee, Keler, Tibor, Davis, Tom, Crowley, Elizabeth, Salazar, Andres, Brody, Joshua, Monjazeb, Arta, Daly, Megan E., Riess, Jonathan, Li, Tianhong, Murphy, William J., Kelly, Karen, Hu, Zhiwei, Shen, Rulong, Campbell, Amanda, McMichael, Elizabeth, Yu, Lianbo, Ramaswam, Bhuvaneswari, London, Cheryl A., Xu, Tian, Carson, William, Kokolus, Kathleen M., Repasky, Elizabeth A., Schell, Todd D., Drabick, Joseph D., Messenheimer, David J., Jensen, Shawn, Rubinstein, Mark, Andrijauskaite, Kristina, Swiderska-syn, Marzena, Lind, Kristin, Choppin, Agnes, Roell, Marina K., Wrangle, John, Rhode, Peter, Wong, Hing, Ahmad, Shamim, Webb, Mason, Abu-Eid, Rasha, Shrimali, Rajeev, Verma, Vivek, Doroodchi, Atbin, Berrong, Zuzana, Yashar, David, Samara, Raed, Mkrtichyan, Mikayel, Khleif, Samir, Powell, Steven, Gitau, Mark, Sumey, Christopher, Terrell, Andrew, Lohr, Michele, Nowak, Ryan K., McGraw, Steven, Jensen, Ash, Blanchard, Miran, Gold, Kathryn A., Cohen, Ezra E. W., Ellison, Christie, Black, Lora, Lee, John, Spanos, William Chad, Wennerberg, Erik, Schwitzer, Emily, Lhuillier, Claire, Koelwyn, Graeme, Hiner, Rebecca, Jones, Lee, Demaria, Sandra, Amanda, Vandeveer, Greiner, John W., Schlom, Jeffrey, Bookstaver, Michelle, Jewell, Christopher M., Gunderson, Andrew, Boulmay, Brian, Li, Rui, Spieler, Bradley, Happel, Kyle, Feng, Zipei, Dubay, Christopher, Fisher, Brenda, Aung, Sandra, Mederos, Eileen, Bifulco, Carlo B., McNamara, Michael, Bahjat, Keith, Redmond, William, Ochoa, Augusto, Hu, Hong-Ming, Mehta, Adi, Lund-Johansen, Fridtjof, Bedu-Addo, Frank, Conn, Greg, King, Michael, Dutta, Panna, Shepard, Robert, Einstein, Mark, Adams, Sylvia, Wang, Ena, Jin, Ping, Novik, Yelena, Morrison, Debra, Oratz, Ruth, Marincola, Franco M., Stroncek, David, Goldberg, Judith, Formenti, Silvia C., Galon, Jérôme, Mlecnik, Bernhard, Marliot, Florence, Ou, Fang-Shu, Lugli, Alessandro, Zlobec, Inti, Rau, Tilman T., Nagtegaal, Iris D., Vink-Borger, Elisa, Hartmann, Arndt, Geppert, Carol, Roehrl, Michael H., Bavi, Prashant, Ohashi, Pamela S., Wang, Julia Y., Nguyen, Linh T., Han, SeongJun, MacGregor, Heather L., Hafezi-Bakhtiari, Sara, Wouters, Bradley G., Kawakami, Yutaka, Papivanova, Boryana, Xu, Mingli, Fujita, Tomonobu, Hazama, Shoichi, Suzuki, Nobuaki, Nagano, Hiroaki, Okuno, Kiyotaka, Itoh, Kyogo, Zavadova, Eva, Vocka, Michal, Spacek, Jan, Petruzelka, Lubos, Konopasek, Bohuslav, Dundr, Pavel, Skalova, Helena, Torigoe, Toshihiko, Sato, Noriyuki, Furuhata, Tomohisa, Takemasa, Ichiro, Van den Eynde, Marc, Jouret-Mourin, Anne, Machiels, Jean-Pascal, Fredriksen, Tessa, Lafontaine, Lucie, Buttard, Bénédicte, Church, Sarah, Maby, Pauline, Angell, Helen, Angelova, Mihaela, Vasaturo, Angela, Bindea, Gabriela, Berger, Anne, Lagorce, Christine, Patel, Prabhu S., Vora, Hemangini H., Shah, Birva, Patel, Jayendrakumar B., Rajvik, Kruti N., Pandya, Shashank J., Shukla, Shilin N., Wang, Yili, Zhang, Guanjun, Masucci, Giuseppe V., Andersson, Emilia K., Grizzi, Fabio, Laghi, Luigi, Botti, Gerardo, Tatangelo, Fabiana, Delrio, Paolo, Cilberto, Gennaro, Marincola, Franco, Sargent, Daniel J., Fox, Bernard A., Algazi, Alain, Tsai, Katy, Rosenblum, Michael, Nandoskar, Prachi, Li, Amy, Nonomura, John, Takamura, Kathryn, Dwyer, Mary, Browning, Erica, Talia, Reneta, Twitty, Chris, Gargosky, Sharron, Campbell, Jean, Le, Mai, Pierce, Robert H., Daud, Adil, Gartrell, Robyn, Marks, Douglas, Stack, Edward, Lu, Yan, Izaki, Daisuke, Beck, Kristen, Jia, Dan Tong, Armenta, Paul, White-Stern, Ashley, Fu, Yichun, Blake, Zoe, Taback, Bret, Horst, Basil, Saenger, Yvonne M., Leonardo, Steven, Gorden, Keith, Fulton, Ross B., Fraser, Kathryn, Kangas, Takashi O., Walsh, Richard, Ertelt, Kathleen, Graff, Jeremy, Uhlik, Mark, Sims, Jennifer S., Lei, Liang, Tsujiuchi, Takashi, Bruce, Jeffrey N., Canoll, Peter, Tolcher, Anthony W, Alley, Evan W, Chichili, Gurunadh, Canoll, Jan E, Moore, Paul, Bonvini, Ezio, Johnson, Syd, Shankar, Sadhna, Vasselli, James, Wigginton, Jon, and Powderly, John

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