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| 1 | Decoupling of DNA damage response signaling from DNA damages underlies temozolomide resistance in glioblastoma cells显示文摘Glioblastoma multiforme (GBM) is the most aggressive primary brain tumor in adults.Current therapy includes surgery,radiation and chemotherapy with temozolomide (TMZ).Major determinants of clinical response to TMZ include methylation status of the O6-methylguanine-DNA methyltransferase (MGMT) promoter and mismatch repair (MMR) status.Though the MGMT promoter is methylated in 45% of cases,for the first nine months of follow-up,TMZ does not change survival outcome.Furthermore,MMR deficiency makes little contribution to clinical resistance,suggesting that there exist unrecognized mechanisms of resistance.We generated paired GBM cell lines whose resistance was attributed to neither MGMT nor MMR.We show that,responding to TMZ,these cells exhibit a decoupling of DNA damage response (DDR) from ongoing DNA damages.They display methylation-resistant synthesis in which ongoing DNA synthesis is not inhibited.They are also defective in the activation of the S and G2 phase checkpoint.DDR proteins ATM,Chk2,MDC1,NBS1 and gammaH2AX also fail to form discrete foci.These results demonstrate that failure of DDR may play an active role in chemoresistance to TMZ.DNA damages by TMZ are repaired by MMR proteins in a futile,reiterative process,which activates DDR signaling network that ultimately leads to the onset of cell death.GBM cells may survive genetic insults in the absence of DDR.We anticipate that our findings will lead to more studies that seek to further define the role of DDR in ultimately determining the fate of a tumor cell in response to TMZ and other DNA methylators. | Stewart P.Johnson Nancy Bullock Francis Ali Osman Darell D.Bigner Henry S.Friedman | 2010 | The Journal of Biomedical Research2010，24，6： | 6 |
| 2 | Management of patients with severe sepsis,treated by drotrecogin alfa(activated)显示文摘 | Pierre-Francois L Darell H | 2002 | Am J Surg2002，，： | 1 |
| 3 | World cities as hegemonic projects: the politics of global imagineering in Montreal显示文摘 | Darel E. Paul | 2004 | Political Geography2004，，5： | 1 |
| 4 | Eetection of DNA and RNA plant viruses by PCR and RT-PCR using a rapid virus release protocol without tissue homogenization显示文摘 | THOMSON DARELLE DIETZGEN G R | 1995 | Journal of Virological Methods1995，54，： | 1 |
| 5 | O6-Benzylguanine-mediated enhancement of nitrosourea activity in Mer? central nervous system tumor xenografts – implications for clinical trials显示文摘 | Stephen T. Keir M. Eileen Dolan Anthony E. Pegg Amy Lawless Robert C. Moschel Darell D. Bigner Henry S. Friedman | 2000 | Cancer Chemotherapy and Pharmacology2000，，6： | 1 |
| 6 | Efficient direction-finding methods employing Forward/Backward averaging显示文摘 | Darel A L Ronald D D Eric M D | 1994 | IEEE Transactions on Signal Processing1994，42，8： | 1 |
| 7 | Growth, morphology, and serial transplantation of anaplastic human gliomas in athymic mice显示文摘 | S. Clifford Schold Dennis E. Bullard Sandra H. Bigner Trevor R. Jones Darell D. Bigner | 1983 | Journal of Neuro - Oncology1983，，1： | 1 |
| 8 | Bispecific antibodies engage T cells for antitumor immunotherapy显示文摘 | Bryan D Choi Mingqing Cai Darell D Bigner Ankit I Mehta Chien-Tsun Kuan John H Sampson | 2011 | Expert Opinion on Biological Therapy2011，，7： | 1 |
| 9 | SIBS-a job shop simulation based scheduler显示文摘 | Darel E M Zvifeuer | 1992 | Computer Integrated Manufacturing Systems1992，2，1： | 1 |
| 10 | Efficient direction-finding methods employing forward backward averaging显示文摘 | Darel A L Ronald D D Eric M D | 1994 | IEEE Transactions on Signal Processing1994，42，8： | 1 |
| 11 | quality evaluation of nitride bonded silicon carbide sidelinling materials显示文摘 | Egil Skybakrmen Lisbet I Sloen Jannicke H Kvello Ove Darell | 2005 | Light Metals2005，，： | 1 |
| 12 | Progress Report of a Phase I Study of the Intracerebral Microinfusion of a Recombinant Chimeric Protein Composed of Transforming Growth Factor (TGF)-α and a Mutated form of the Pseudomonas Exotoxin Termed PE-38 (TP-38) for the Treatment of Malignant Brain显示文摘 | John H. Sampson Gamal Akabani Gary E. Archer Darell D. Bigner Mitchel S. Berger Allan H. Friedman Henry S. Friedman James E. Herndon II Sandeep Kunwar Steve Marcus Roger E. McLendon Alison Paolino Kara Penne James Provenzale Jennifer Quinn David A. Reardo | 2003 | Journal of Neuro - Oncology2003，，1： | 1 |
| 13 | An Introduction to TPJZ: The Theory of Inventive Problem Solving 显示文摘 | Darell Mare | 2001 | Creativity and Innovation Management2001，，2： | 1 |
| 14 | A sphingosine kinase inhibitor induces cell death in temozolomide resistant glioblastoma cells显示文摘 | Meryem Bektas Stewart P. Johnson William E. Poe Darell D. Bigner Henry S. Friedman | 2009 | Cancer Chemotherapy and Pharmacology2009，，： | 1 |
| 15 | Immunotoxin Therapy for Lung Cancer显示文摘 | Li-Yi Xie Hai-Lan Piao Min Fan Zhen Zhang Chen Wang Darell D Bigner Xu-Hui Bao | 2017 | Chinese Medical Journal2017，，5： | 0 |
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