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357 results on '"McConkey, D"'

1. Comprehensive molecular characterization of urothelial bladder carcinoma

Author

Taylor, Barry, Weinstein, JN, Akbani, R, Broom, BM, Wang, W, Verhaak, RGW, McConkey, D, Lerner, S, Morgan, M, Creighton, CJ, and Smith, C

Abstract

Urothelial carcinoma of the bladder is a common malignancy that causes approximately 150,000 deaths per year worldwide. So far, no molecularly targeted agents have been approved for treatment of the disease. As part of The Cancer Genome Atlas project, we r

Published
2014

6. Calcium and Cyclosporin A in the Regulation of Apoptosis

Author

McConkey, D. J., Orrenius, S., Capron, A., editor, Compans, R. W., editor, Cooper, M., editor, Koprowski, H., editor, McConnell, I., editor, Melchers, F., editor, Oldstone, M., editor, Olsnes, S., editor, Potter, M., editor, Saedler, H., editor, Vogt, P. K., editor, Wagner, H., editor, Wilson, I., editor, Kroemer, Guido, editor, and Martinez-A., Carlos, editor

Published
1995
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7. Thymocyte Apoptosis by Glucocorticoids and cAMP

Author

Jondal, M., Xue, Y., McConkey, D. J., Okret, S., Capron, A., editor, Compans, R. W., editor, Cooper, M., editor, Koprowski, H., editor, McConnell, I., editor, Melchers, F., editor, Oldstone, M., editor, Olsnes, S., editor, Potter, M., editor, Saedler, H., editor, Vogt, P. K., editor, Wagner, H., editor, Wilson, I., editor, Kroemer, Guido, editor, and Martinez-A., Carlos, editor

Published
1995
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15. Epigenetic profiling demarcates molecular subtypes of muscle-invasive bladder cancer

Author

van der Vos, K.E. (author), Vis, D.J. (author), Nevedomskaya, E. (author), Kim, Y. (author), Choi, W. (author), McConkey, D. (author), Wessels, L.F.A. (author), van Rhijn, B.W.G. (author), Zwart, W. (author), van der Heijden, M.S. (author), van der Vos, K.E. (author), Vis, D.J. (author), Nevedomskaya, E. (author), Kim, Y. (author), Choi, W. (author), McConkey, D. (author), Wessels, L.F.A. (author), van Rhijn, B.W.G. (author), Zwart, W. (author), and van der Heijden, M.S. (author)

Abstract

Muscle-invasive bladder cancer (MIBC) is a heterogeneous disease that often recurs despite aggressive treatment with neoadjuvant chemotherapy and (radical) cystectomy. Basal and luminal molecular subtypes have been identified that are linked to clinical characteristics and have differential sensitivities to chemotherapy. While it has been suggested that epigenetic mechanisms play a role in defining these subtypes, a thorough understanding of the biological mechanisms is lacking. This report details the first genome-wide analysis of histone methylation patterns of human primary bladder tumours by chromatin immunoprecipitations and next-generation sequencing (ChIP-seq). We profiled multiple histone marks: H3K27me3, a marker for repressed genes, and H3K4me1 and H3K4me3, which are indicators of active enhancers and active promoters. Integrated analysis of ChIP-seq data and RNA sequencing revealed that H3K4 mono-methylation demarcates MIBC subtypes, while no association was found for the other two histone modifications in relation to basal and luminal subtypes. Additionally, we identified differentially methylated H3K4me1 peaks in basal and luminal tumour samples, suggesting that active enhancers play a role in defining subtypes. Our study is the first analysis of histone modifications in primary bladder cancer tissue and provides an important resource for the bladder cancer community., Pattern Recognition and Bioinformatics

Published
2020
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18. Recombinant BCG overexpressing STING agonist elicits trained immunity and improved antitumor efficacy in non-muscle invasive bladder cancer

Author

Singh, AK, primary, Praharaj, M, additional, Lombardo, KA, additional, Yoshida, T, additional, Matoso, A, additional, Baras, AS, additional, Zhao, L, additional, Prasad, P, additional, Srikrishna, G, additional, Powell, JD, additional, Kates, M, additional, McConkey, D, additional, Pardoll, DM, additional, Bishai, WR, additional, and Bivalacqua, TJ, additional

Published
2020
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25. Summary and Recommendations from the National Cancer Institute’s Clinical Trials Planning Meeting on Novel Therapeutics for Non-Muscle Invasive Bladder Cancer

Author

Lerner, SP, Bajorin, DF, Dinney, CP, Efstathiou, JA, Groshen, S, Hahn, NM, Kwiatkowski, D, O'Donnell, M, Rosenberg, J, Svatek, R, Abrams, JS, Al-Ahmadie, H, Apolo, AB, Bellmunt, J, Callahan, M, Cha, EK, Drake, C, Jarrow, J, Kamat, A, Kim, W, Knowles, M, Mann, B, Marchioni, L, McConkey, D, McShane, L, Ramirez, N, Sharabi, A, Sharpe, AH, Solit, D, Tangen, CM, Amini, AT, Van Allen, E, West, PJ, Witjes, JA, and Quale, DZ

Abstract

The NCI Bladder Cancer Task Force convened a Clinical Trials Planning Meeting (CTPM) Workshop focused on Novel Therapeutics for Non-Muscle Invasive Bladder Cancer (NMIBC). Meeting attendees included a broad and multi-disciplinary group of clinical and research stakeholders and included leaders from NCI, FDA, National Clinical Trials Network (NCTN), advocacy and the pharmaceutical and biotech industry. The meeting goals and objectives were to: 1) create a collaborative environment in which the greater bladder research community can pursue future optimally designed novel clinical trials focused on the theme of molecular targeted and immune-based therapies in NMIBC; 2) frame the clinical and translational questions that are of highest priority; and 3) develop two clinical trial designs focusing on immunotherapy and molecular targeted therapy. Despite successful development and implementation of large Phase II and Phase III trials in bladder and upper urinary tract cancers, there are no active and accruing trials in the NMIBC space within the NCTN. Disappointingly, there has been only one new FDA approved drug (Valrubicin) in any bladder cancer disease state since 1998. Although genomic-based data for bladder cancer are increasingly available, translating these discoveries into practice changing treatment is still to come. Recently, major efforts in defining the genomic characteristics of NMIBC have been achieved. Aligned with these data is the growing number of targeted therapy agents approved and/or in development in other organ site cancers and the multiple similarities of bladder cancer with molecular subtypes in these other cancers. Additionally, although bladder cancer is one of the more immunogenic tumors, some tumors have the ability to attenuate or eliminate host immune responses. Two trial concepts emerged from the meeting including a window of opportunity trial (Phase 0) testing an FGFR3 inhibitor and a second multi-arm multi-stage trial testing combinations of BCG or radiotherapy and immunomodulatory agents in patients who recur after induction BCG (BCG failure).

Published
2016

28. Muscle invasive bladder cancer: A single sample patient assay to predict molecular subtypes and benefit of neoadjuvant chemotherapy

Author

Seiler, R., primary, Ashab, H.A.D., additional, Erho, N., additional, Van Rhijn, B.W., additional, Winters, B., additional, Douglas, J., additional, Van Kessel, K., additional, Fransen Van De Putte, E., additional, Sommerlad, M., additional, Wang, Q., additional, Choeurng, V., additional, Gibb, E., additional, Palmer-Aronsten, B., additional, Lam, L., additional, Buerki, C., additional, Davicioni, E., additional, Sjödahl, G., additional, Kardos, J., additional, Hoadley, K., additional, Lerner, S., additional, McConkey, D., additional, Choi, W., additional, Kim, W., additional, Kiss, B., additional, Thalmann, G., additional, Todenhöfer, T., additional, Crabb, S., additional, North, S., additional, Zwarthoff, E., additional, Boormans, J., additional, Wright, J., additional, Dall’Era, M., additional, Van Der Heijden, M., additional, and Black, P., additional

Published
2017
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29. Pharmacodynamic Analysis of Target Inhibition and Endothelial Cell Death in Tumors Treated with the Vascular Endothelial Growth Factor Receptor Antagonists SU5416 or SU6668

Author

Davis, D. W., Takamori, R., Raut, C. P., Xiong, H. Q., Herbst, R. S., Stadler, W. M., Heymach, J. V., Demetri, G. D., Rashid, A., Shen, Y., Sijin Wen, Abbruzzese, J. L., and Mcconkey, D. J.

Subjects
Cancer Research, Oncology
Abstract

Purpose: To determine the effects of small molecule inhibitors of vascular endothelial growth factor receptor (VEGFR)-2 (SU5416 and SU6668) on receptor phosphorylation in tumor xenografts and in paired tumor biopsies obtained in three clinical trials in patients with advanced solid malignancies. Experimental Design: The dose-dependent effects of SU6668 on angiogenesis and tumor growth were investigated in orthotopic L3.6pl pancreatic tumors. Excisional or 18G core biopsies were obtained from patients before and after therapy with SU5416 or SU6668. Laser scanning cytometry–mediated analysis was used to quantify levels of phosphorylated and total VEGFRs and platelet-derived growth factor receptors (PDGFR), tumor microvessel densities, vessel sizes, and endothelial and tumor cell apoptosis. Results: Significant inhibition of tumor microvessel density and growth and increased apoptosis were observed at SU6668 maximum tolerated dose (100 mg/kg) in L3.6pl xenografts. At 6 hours post therapy, SU6668 reduced VEGFR and PDGFR phosphorylation in the tumors by 50% and 92%, respectively, but levels rebounded beyond the baselines by 24 hours. Levels of phosphorylated VEGFR-2 and PDGFR also decreased significantly (≈50%) 6 hours after therapy in 1 of 6 primary human tumors treated with SU6668, but these effects were not associated with increased apoptosis. A significant increase in endothelial cell apoptosis was observed in one tumor exposed to SU5416 and was associated with an increase in vessel size, but these changes occurred without an increase in tumor cell death. Conclusions: SU5416 and SU6668 displayed biological activity in xenografts. However, neither drug produced marked biological activity in primary patient tumors.

Published
2005

30. Summary and Recommendations from the National Cancer Institute's Clinical Trials Planning Meeting on Novel Therapeutics for Non-Muscle Invasive Bladder Cancer

Author

Lerner, S.P., Bajorin, D.F., Dinney, C.P., Efstathiou, J.A., Groshen, S., Hahn, N.M., Hansel, D., Kwiatkowski, D., O'Donnell, M., Rosenberg, J., Svatek, R., Abrams, J.S., Al-Ahmadie, H., Apolo, A.B., Bellmunt, J., Callahan, M., Cha, E.K., Drake, C., Jarow, J., Kamat, A., Kim, W., Knowles, M., Mann, B., Marchionni, L., McConkey, D., McShane, L., Ramirez, N., Sharabi, A., Sharpe, A.H., Solit, D., Tangen, C.M., Amiri, A.T., Allen, E. Van, West, P.J., Witjes, J.A., Quale, D.Z., Lerner, S.P., Bajorin, D.F., Dinney, C.P., Efstathiou, J.A., Groshen, S., Hahn, N.M., Hansel, D., Kwiatkowski, D., O'Donnell, M., Rosenberg, J., Svatek, R., Abrams, J.S., Al-Ahmadie, H., Apolo, A.B., Bellmunt, J., Callahan, M., Cha, E.K., Drake, C., Jarow, J., Kamat, A., Kim, W., Knowles, M., Mann, B., Marchionni, L., McConkey, D., McShane, L., Ramirez, N., Sharabi, A., Sharpe, A.H., Solit, D., Tangen, C.M., Amiri, A.T., Allen, E. Van, West, P.J., Witjes, J.A., and Quale, D.Z.

Abstract

Contains fulltext : 171566.pdf (Publisher’s version ) (Open Access), The NCI Bladder Cancer Task Force convened a Clinical Trials Planning Meeting (CTPM) Workshop focused on Novel Therapeutics for Non-Muscle Invasive Bladder Cancer (NMIBC). Meeting attendees included a broad and multi-disciplinary group of clinical and research stakeholders and included leaders from NCI, FDA, National Clinical Trials Network (NCTN), advocacy and the pharmaceutical and biotech industry. The meeting goals and objectives were to: 1) create a collaborative environment in which the greater bladder research community can pursue future optimally designed novel clinical trials focused on the theme of molecular targeted and immune-based therapies in NMIBC; 2) frame the clinical and translational questions that are of highest priority; and 3) develop two clinical trial designs focusing on immunotherapy and molecular targeted therapy. Despite successful development and implementation of large Phase II and Phase III trials in bladder and upper urinary tract cancers, there are no active and accruing trials in the NMIBC space within the NCTN. Disappointingly, there has been only one new FDA approved drug (Valrubicin) in any bladder cancer disease state since 1998. Although genomic-based data for bladder cancer are increasingly available, translating these discoveries into practice changing treatment is still to come. Recently, major efforts in defining the genomic characteristics of NMIBC have been achieved. Aligned with these data is the growing number of targeted therapy agents approved and/or in development in other organ site cancers and the multiple similarities of bladder cancer with molecular subtypes in these other cancers. Additionally, although bladder cancer is one of the more immunogenic tumors, some tumors have the ability to attenuate or eliminate host immune responses. Two trial concepts emerged from the meeting including a window of opportunity trial (Phase 0) testing an FGFR3 inhibitor and a second multi-arm multi-stage trial testing combinations

Published
2016

34. 901 - Muscle invasive bladder cancer: A single sample patient assay to predict molecular subtypes and benefit of neoadjuvant chemotherapy

Author

Seiler, R., Ashab, H.A.D., Erho, N., Van Rhijn, B.W., Winters, B., Douglas, J., Van Kessel, K., Fransen Van De Putte, E., Sommerlad, M., Wang, Q., Choeurng, V., Gibb, E., Palmer-Aronsten, B., Lam, L., Buerki, C., Davicioni, E., Sjödahl, G., Kardos, J., Hoadley, K., Lerner, S., McConkey, D., Choi, W., Kim, W., Kiss, B., Thalmann, G., Todenhöfer, T., Crabb, S., North, S., Zwarthoff, E., Boormans, J., Wright, J., Dall’Era, M., Van Der Heijden, M., and Black, P.

Published
2017
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39. Use of P63 expression to define a lethal subset of muscle-invasive bladder cancers.

Author

Choi, W., primary, Shah, J. B., additional, Tran, M., additional, Svatek, R. S., additional, Marquis, L., additional, Lee, I. C., additional, Yu, D., additional, Adam, L., additional, Bondaruk, J. E., additional, Wen, S., additional, Shen, Y., additional, Dinney, C. P. N., additional, Czerniak, B., additional, McConkey, D. J., additional, and Siefker-Radtke, A. O., additional

Published
2011
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41. Marizomib, a Proteasome Inhibitor for All Seasons: Preclinical Profile and a Framework for Clinical Trials

Author

C. Potts, B., primary, X. Albitar, M., additional, C. Anderson, K., additional, Baritaki, S., additional, Berkers, C., additional, Bonavida, B., additional, Chandra, J., additional, Chauhan, D., additional, C. Cusack, J., additional, Fenical, W., additional, M. Ghobrial, I., additional, Groll, M., additional, R. Jensen, P., additional, S. Lam, K., additional, K. Lloyd, G., additional, McBride, W., additional, J. McConkey, D., additional, P. Miller, C., additional, T.C. Neuteboom, S., additional, Oki, Y., additional, Ovaa, H., additional, Pajonk, F., additional, G. Richardson, P., additional, M. Roccaro, A., additional, M. Sloss, C., additional, A. Spear, M., additional, Valashi, E., additional, Younes, A., additional, and A. Palladino, M., additional

Published
2011
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46. Phase II trial of imatinib mesylate in patients with metastatic melanoma

Author

Kim, K B, primary, Eton, O, additional, Davis, D W, additional, Frazier, M L, additional, McConkey, D J, additional, Diwan, A H, additional, Papadopoulos, N E, additional, Bedikian, A Y, additional, Camacho, L H, additional, Ross, M I, additional, Cormier, J N, additional, Gershenwald, J E, additional, Lee, J E, additional, Mansfield, P F, additional, Billings, L A, additional, Ng, C S, additional, Charnsangavej, C, additional, Bar-Eli, M, additional, Johnson, M M, additional, Murgo, A J, additional, and Prieto, V G, additional

Published
2008
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