MGMT Gene Silencing and Benefit from Temozolomide in Glioblastoma
Monika E. Hegi, Ph.D., Annie-Claire Diserens, M.Sc., Thierry Gorlia, M.Sc., Marie-France Hamou, Nicolas de Tribolet, M.D., Michael Weller, M.D., Johan M. Kros, M.D., Johannes A. Hainfellner, M.D., Warren Mason, M.D., Luigi Mariani, M.D., Jacoline E.C. Bromberg, M.D., Peter Hau, M.D., René O. Mirimanoff, M.D., J. Gregory Cairncross, M.D., Robert C. Janzer, M.D., and Roger Stupp, M.D.
Background Epigenetic silencing of the MGMT (O6-methylguanine–DNAmethyltransferase) DNA-repair gene by promoter methylation compromisesDNA repair and has been associated with longer survival in patientswith glioblastoma who receive alkylating agents.
Methods We tested the relationship between MGMT silencing inthe tumor and the survival of patients who were enrolled ina randomized trial comparing radiotherapy alone with radiotherapycombined with concomitant and adjuvant treatment with temozolomide.The methylation status of the MGMT promoter was determined bymethylation-specific polymerase-chain-reaction analysis.
Results The MGMT promoter was methylated in 45 percent of 206assessable cases. Irrespective of treatment, MGMT promoter methylationwas an independent favorable prognostic factor (P<0.001 bythe log-rank test; hazard ratio, 0.45; 95 percent confidenceinterval, 0.32 to 0.61). Among patients whose tumor containeda methylated MGMT promoter, a survival benefit was observedin patients treated with temozolomide and radiotherapy; theirmedian survival was 21.7 months (95 percent confidence interval,17.4 to 30.4), as compared with 15.3 months (95 percent confidenceinterval, 13.0 to 20.9) among those who were assigned to onlyradiotherapy (P=0.007 by the log-rank test). In the absenceof methylation of the MGMT promoter, there was a smaller andstatistically insignificant difference in survival between thetreatment groups.
Conclusions Patients with glioblastoma containing a methylatedMGMT promoter benefited from temozolomide, whereas those whodid not have a methylated MGMT promoter did not have such abenefit.
Source Information
From the Laboratory of Tumor Biology and Genetics, Department of Neurosurgery (M.E.H., A.-C.D., M.-F.H., N.T.), the Departments of Radiotherapy (R.O.M.) and Neuropathology (R.C.J.), and the Multidisciplinary Oncology Center (R.S.), University Hospital Lausanne, Lausanne; the Department of Neurosurgery, University Hospital Geneva, Geneva (N.T.); the National Center of Competence in Research Molecular Oncology, Swiss Institute for Experimental Cancer Research, Epalinges (M.E.H.); and the Department of Neurosurgery, Inselspital, Bern (L.M.) — all in Switzerland; the Data Center, European Organisation for Research and Treatment of Cancer, Brussels (T.G.); the Department of Neurology, University of Tübingen, Tübingen (M.W.), and the Department of Neurology, University of Regensburg, Regensburg (P.H.) — both in Germany; the Division of Neuropathology, University Hospital Rotterdam, Rotterdam (J.M.K.), and University Medical Center, Utrecht (J.E.C.B.) — both in the Netherlands; the Institute of Neurology, Medical University of Vienna, Vienna, (J.A.H.); and Princess Margaret Hospital, Toronto (W.M.), and the University of Calgary, Calgary, Alta. (J.G.C.) — both in Canada.
Address reprint requests to Dr. Hegi at the Laboratory of Tumor Biology and Genetics, Department of Neurosurgery, University Hospital (CHUV), BH19-110, 1011 Lausanne, Switzerland, or at monika.hegi{at}chuv.hospvd.ch.
Treatment of Brain Tumors
Paulino A. C., Teh B. S., Sadeh M., Seiter K., Ashby L., LaRocca R., Ryken T., Aiken R. D., Rutkowski S., Ottensmeier H., Pietsch T., Stupp R., Hegi M. E., DeAngelis L. M.
Extract |
Full Text |
PDF
N Engl J Med 2005;
352:2350-2353, Jun 2, 2005.
Correspondence
This article has been cited by other articles:
Gan, H. K., Rosenthal, M. A., Dowling, A., Kalnins, R., Algar, E., Wong, N., Benson, A., Woods, A.-M., Cher, L.
(2010). A phase II trial of primary temozolomide in patients with grade III oligodendroglial brain tumors. Neuro Oncology
0: nop065v1-nop065
[Abstract][Full Text]
Rivera, A. L., Pelloski, C. E., Gilbert, M. R., Colman, H., De La Cruz, C., Sulman, E. P., Bekele, B. N., Aldape, K. D.
(2010). MGMT promoter methylation is predictive of response to radiotherapy and prognostic in the absence of adjuvant alkylating chemotherapy for glioblastoma. Neuro Oncology
12: 116-121
[Abstract][Full Text]
Song, H.-R., Gonzalez-Gomez, I., Suh, G. S., Commins, D. L., Sposto, R., Gilles, F. H., Deneen, B., Erdreich-Epstein, A.
(2010). Nuclear factor IA is expressed in astrocytomas and is associated with improved survival. Neuro Oncology
12: 122-132
[Abstract][Full Text]
Lavon, I., Refael, M., Zelikovitch, B., Shalom, E., Siegal, T.
(2010). Serum DNA can define tumor-specific genetic and epigenetic markers in gliomas of various grades. Neuro Oncology
12: 173-180
[Abstract][Full Text]
Brandes, A. A., Franceschi, E., Tosoni, A., Bartolini, S., Bacci, A., Agati, R., Ghimenton, C., Turazzi, S., Talacchi, A., Skrap, M., Marucci, G., Volpin, L., Morandi, L., Pizzolitto, S., Gardiman, M., Andreoli, A., Calbucci, F., Ermani, M.
(2010). O6-methylguanine DNA-methyltransferase methylation status can change between first surgery for newly diagnosed glioblastoma and second surgery for recurrence: clinical implications. Neuro Oncology
: nop050v1-nop050
[Abstract][Full Text]
Costa, B. M., Smith, J. S., Chen, Y., Chen, J., Phillips, H. S., Aldape, K. D., Zardo, G., Nigro, J., James, C. D., Fridlyand, J., Reis, R. M., Costello, J. F.
(2010). Reversing HOXA9 Oncogene Activation by PI3K Inhibition: Epigenetic Mechanism and Prognostic Significance in Human Glioblastoma. Cancer Res.
70: 453-462
[Abstract][Full Text]
Shah, G. D., Socci, N. D., Gold, J. S., Wolchok, J. D., Carvajal, R. D., Panageas, K. S., Viale, A., Brady, M. S., Coit, D. G., Chapman, P. B.
(2010). Phase II trial of neoadjuvant temozolomide in resectable melanoma patients. Ann Oncol
0: mdp593v1-mdp593
[Abstract][Full Text]
Watson, A. J., Sabharwal, A., Thorncroft, M., McGown, G., Kerr, R., Bojanic, S., Soonawalla, Z., King, A., Miller, A., Waller, S., Leung, H., Margison, G. P., Middleton, M. R.
(2010). Tumor O6-methylguanine-DNA Methyltransferase Inactivation by Oral Lomeguatrib. Clin. Cancer Res.
16: 743-749
[Abstract][Full Text]
Grzendowski, M., Wolter, M., Riemenschneider, M. J., Knobbe, C. B., Schlegel, U., Meyer, H. E., Reifenberger, G., Stuhler, K.
(2010). Differential proteome analysis of human gliomas stratified for loss of heterozygosity on chromosomal arms 1p and 19q. Neuro Oncology
0: nop025v2-nop025
[Abstract][Full Text]
Lim, D. H K, Maher, E. R
(2010). DNA methylation: a form of epigenetic control of gene expression. The Obstetrician and Gynaecologist
12: 37-42
[Abstract][Full Text]
Spiegl-Kreinecker, S., Pirker, C., Filipits, M., Lotsch, D., Buchroithner, J., Pichler, J., Silye, R., Weis, S., Micksche, M., Fischer, J., Berger, W.
(2010). O6-Methylguanine DNA methyltransferase protein expression in tumor cells predicts outcome of temozolomide therapy in glioblastoma patients. Neuro Oncology
12: 28-36
[Abstract][Full Text]
Colman, H., Zhang, L., Sulman, E. P., McDonald, J. M., Shooshtari, N. L., Rivera, A., Popoff, S., Nutt, C. L., Louis, D. N., Cairncross, J. G., Gilbert, M. R., Phillips, H. S., Mehta, M. P., Chakravarti, A., Pelloski, C. E., Bhat, K., Feuerstein, B. G., Jenkins, R. B., Aldape, K.
(2010). A multigene predictor of outcome in glioblastoma. Neuro Oncology
12: 49-57
[Abstract][Full Text]
Wick, W., Hartmann, C., Engel, C., Stoffels, M., Felsberg, J., Stockhammer, F., Sabel, M. C., Koeppen, S., Ketter, R., Meyermann, R., Rapp, M., Meisner, C., Kortmann, R. D., Pietsch, T., Wiestler, O. D., Ernemann, U., Bamberg, M., Reifenberger, G., von Deimling, A., Weller, M.
(2009). NOA-04 Randomized Phase III Trial of Sequential Radiochemotherapy of Anaplastic Glioma With Procarbazine, Lomustine, and Vincristine or Temozolomide. JCO
27: 5874-5880
[Abstract][Full Text]
van den Bent, M. J., Dubbink, H. J., Sanson, M., van der Lee-Haarloo, C. R., Hegi, M., Jeuken, J. W.M., Ibdaih, A., Brandes, A. A., Taphoorn, M. J.B., Frenay, M., Lacombe, D., Gorlia, T., Dinjens, W. N.M., Kros, J. M.
(2009). MGMT Promoter Methylation Is Prognostic but Not Predictive for Outcome to Adjuvant PCV Chemotherapy in Anaplastic Oligodendroglial Tumors: A Report From EORTC Brain Tumor Group Study 26951. JCO
27: 5881-5886
[Abstract][Full Text]
DeAngelis, L. M.
(2009). Anaplastic Gliomas. JCO
27: 5861-5862
[Full Text]
Weller, M., Felsberg, J., Hartmann, C., Berger, H., Steinbach, J. P., Schramm, J., Westphal, M., Schackert, G., Simon, M., Tonn, J. C., Heese, O., Krex, D., Nikkhah, G., Pietsch, T., Wiestler, O., Reifenberger, G., von Deimling, A., Loeffler, M.
(2009). Molecular Predictors of Progression-Free and Overall Survival in Patients With Newly Diagnosed Glioblastoma: A Prospective Translational Study of the German Glioma Network. JCO
27: 5743-5750
[Abstract][Full Text]
Kouwenhoven, M. C.M., Gorlia, T., Kros, J. M., Ibdaih, A., Brandes, A. A., Bromberg, J. E.C., Mokhtari, K., van Duinen, S. G., Teepen, J. L., Wesseling, P., Vandenbos, F., Grisold, W., Sipos, L., Mirimanoff, R., Vecht, C. J., Allgeier, A., Lacombe, D., van den Bent, M. J.
(2009). Molecular analysis of anaplastic oligodendroglial tumors in a prospective randomized study: A report from EORTC study 26951. Neuro Oncology
11: 737-746
[Abstract][Full Text]
Maurer, G. D., Tritschler, I., Adams, B., Tabatabai, G., Wick, W., Stupp, R., Weller, M.
(2009). Cilengitide modulates attachment and viability of human glioma cells, but not sensitivity to irradiation or temozolomide in vitro. Neuro Oncology
11: 747-756
[Abstract][Full Text]
Nord, H., Hartmann, C., Andersson, R., Menzel, U., Pfeifer, S., Piotrowski, A., Bogdan, A., Kloc, W., Sandgren, J., Olofsson, T., Hesselager, G., Blomquist, E., Komorowski, J., von Deimling, A., Bruder, C. E.G., Dumanski, J. P., de Stahl, T. D.
(2009). Characterization of novel and complex genomic aberrations in glioblastoma using a 32K BAC array. Neuro Oncology
11: 803-818
[Abstract][Full Text]
Pirzkall, A., McGue, C., Saraswathy, S., Cha, S., Liu, R., Vandenberg, S., Lamborn, K. R., Berger, M. S., Chang, S. M., Nelson, S. J.
(2009). Tumor regrowth between surgery and initiation of adjuvant therapy in patients with newly diagnosed glioblastoma. Neuro Oncology
11: 842-852
[Abstract][Full Text]
MINNITI, G., MUNI, R., LANZETTA, G., MARCHETTI, P., ENRICI, R. M.
(2009). Chemotherapy for Glioblastoma: Current Treatment and Future Perspectives for Cytotoxic and Targeted Agents. Anticancer Res
29: 5171-5184
[Abstract][Full Text]
Gao, Y., Fotovati, A., Lee, C., Wang, M., Cote, G., Guns, E., Toyota, B., Faury, D., Jabado, N., Dunn, S. E.
(2009). Inhibition of Y-box binding protein-1 slows the growth of glioblastoma multiforme and sensitizes to temozolomide independent O6-methylguanine-DNA methyltransferase. Molecular Cancer Therapeutics
8: 3276-3284
[Abstract][Full Text]
Gerstner, E. R., Yip, S., Wang, D. L., Louis, D. N., Iafrate, A. J., Batchelor, T. T.
(2009). MGMT METHYLATION IS A PROGNOSTIC BIOMARKER IN ELDERLY PATIENTS WITH NEWLY DIAGNOSED GLIOBLASTOMA. Neurology
73: 1509-1510
[Full Text]
Fangusaro, J.
(2009). Pediatric High-Grade Gliomas and Diffuse Intrinsic Pontine Gliomas. J Child Neurol
24: 1409-1417
[Abstract]
FUKUSHIMA, T., TAKESHIMA, H., KATAOKA, H.
(2009). Anti-glioma Therapy with Temozolomide and Status of the DNA-Repair Gene MGMT. Anticancer Res
29: 4845-4854
[Abstract][Full Text]
Felsberg, J., Rapp, M., Loeser, S., Fimmers, R., Stummer, W., Goeppert, M., Steiger, H.-J., Friedensdorf, B., Reifenberger, G., Sabel, M. C.
(2009). Prognostic Significance of Molecular Markers and Extent of Resection in Primary Glioblastoma Patients. Clin. Cancer Res.
15: 6683-6693
[Abstract][Full Text]
Lin, Y., Jiang, T., Zhou, K., Xu, L., Chen, B., Li, G., Qiu, X., Jiang, T., Zhang, W., Song, S. W.
(2009). Plasma IGFBP-2 levels predict clinical outcomes of patients with high-grade gliomas. Neuro Oncology
11: 468-476
[Abstract][Full Text]
SHARMA, S., SALEHI, F., SCHEITHAUER, B. W., ROTONDO, F., SYRO, L. V., KOVACS, K.
(2009). Role of MGMT in Tumor Development, Progression, Diagnosis, Treatment and Prognosis. Anticancer Res
29: 3759-3768
[Abstract][Full Text]
ZUSTOVICH, F., LOMBARDI, G., DELLA PUPPA, A., ROTILIO, A., SCIENZA, R., PASTORELLI, D.
(2009). A Phase II Study of Cisplatin and Temozolomide in Heavily Pre-treated Patients with Temozolomide-refractory High-grade Malignant Glioma. Anticancer Res
29: 4275-4279
[Abstract][Full Text]
Ghulam Muhammad, A.K.M., Candolfi, M., King, G. D., Yagiz, K., Foulad, D., Mineharu, Y., Kroeger, K. M., Treuer, K. A., Nichols, W. S., Sanderson, N. S., Yang, J., Khayznikov, M., Van Rooijen, N., Lowenstein, P. R., Castro, M. G.
(2009). Antiglioma Immunological Memory in Response to Conditional Cytotoxic/Immune-Stimulatory Gene Therapy: Humoral and Cellular Immunity Lead to Tumor Regression. Clin. Cancer Res.
15: 6113-6127
[Abstract][Full Text]
Grossman, S. A., Ye, X., Chamberlain, M., Mikkelsen, T., Batchelor, T., Desideri, S., Piantadosi, S., Fisher, J., Fine, H. A.
(2009). Talampanel With Standard Radiation and Temozolomide in Patients With Newly Diagnosed Glioblastoma: A Multicenter Phase II Trial. JCO
27: 4155-4161
[Abstract][Full Text]
Hegi, M. E., Sciuscio, D., Murat, A., Levivier, M., Stupp, R.
(2009). Epigenetic Deregulation of DNA Repair and Its Potential for Therapy. Clin. Cancer Res.
15: 5026-5031
[Abstract][Full Text]
Clarke, J. L., Iwamoto, F. M., Sul, J., Panageas, K., Lassman, A. B., DeAngelis, L. M., Hormigo, A., Nolan, C. P., Gavrilovic, I., Karimi, S., Abrey, L. E.
(2009). Randomized Phase II Trial of Chemoradiotherapy Followed by Either Dose-Dense or Metronomic Temozolomide for Newly Diagnosed Glioblastoma. JCO
27: 3861-3867
[Abstract][Full Text]
Uccella, S, Cerutti, R, Placidi, C, Marchet, S, Carnevali, I, Bernasconi, B, Proserpio, I, Pinotti, G, Tibiletti, M G, Furlan, D, Capella, C
(2009). MGMT methylation in diffuse large B-cell lymphoma: validation of quantitative methylation-specific PCR and comparison with MGMT protein expression. J. Clin. Pathol.
62: 715-723
[Abstract][Full Text]
Everhard, S., Tost, J., El Abdalaoui, H., Criniere, E., Busato, F., Marie, Y., Gut, I. G., Sanson, M., Mokhtari, K., Laigle-Donadey, F., Hoang-Xuan, K., Delattre, J.-Y., Thillet, J.
(2009). Identification of regions correlating MGMT promoter methylation and gene expression in glioblastomas. Neuro Oncology
11: 348-356
[Abstract][Full Text]
Kristensen, L. S., Hansen, L. L.
(2009). PCR-Based Methods for Detecting Single-Locus DNA Methylation Biomarkers in Cancer Diagnostics, Prognostics, and Response to Treatment. Clin. Chem.
55: 1471-1483
[Abstract][Full Text]
Dungey, F. A., Caldecott, K. W., Chalmers, A. J.
(2009). Enhanced radiosensitization of human glioma cells by combining inhibition of poly(ADP-ribose) polymerase with inhibition of heat shock protein 90. Molecular Cancer Therapeutics
8: 2243-2254
[Abstract][Full Text]
Yadav, A. K., Renfrow, J. J., Scholtens, D. M., Xie, H., Duran, G. E., Bredel, C., Vogel, H., Chandler, J. P., Chakravarti, A., Robe, P. A., Das, S., Scheck, A. C., Kessler, J. A., Soares, M. B., Sikic, B. I., Harsh, G. R., Bredel, M.
(2009). Monosomy of Chromosome 10 Associated With Dysregulation of Epidermal Growth Factor Signaling in Glioblastomas. JAMA
302: 276-289
[Abstract][Full Text]
Yip, S., Miao, J., Cahill, D. P., Iafrate, A. J., Aldape, K., Nutt, C. L., Louis, D. N.
(2009). MSH6 Mutations Arise in Glioblastomas during Temozolomide Therapy and Mediate Temozolomide Resistance. Clin. Cancer Res.
15: 4622-4629
[Abstract][Full Text]
MELLAI, M., CALDERA, V., ANNOVAZZI, L., CHIO, A., LANOTTE, M., CASSONI, P., FINOCCHIARO, G., SCHIFFER, D.
(2009). MGMT Promoter Hypermethylation in a Series of 104 Glioblastomas. Cancer Genomics Proteomics
6: 219-227
[Abstract][Full Text]
Frosina, G.
(2009). DNA Repair and Resistance of Gliomas to Chemotherapy and Radiotherapy. Mol Cancer Res
7: 989-999
[Abstract][Full Text]
Sepulveda, A. R., Jones, D., Ogino, S., Samowitz, W., Gulley, M. L., Edwards, R., Levenson, V., Pratt, V. M., Yang, B., Nafa, K., Yan, L., Vitazka, P.
(2009). CpG Methylation Analysis--Current Status of Clinical Assays and Potential Applications in Molecular Diagnostics: A Report of the Association for Molecular Pathology. J. Mol. Diagn.
11: 266-278
[Abstract][Full Text]
FABI, A., RUSSILLO, M., METRO, G., VIDIRI, A., DI GIOVANNI, S., COGNETTI, F.
(2009). Pseudoprogression and MGMT Status in Glioblastoma Patients: Implications in Clinical Practice. Anticancer Res
29: 2607-2610
[Abstract][Full Text]
Candolfi, M., Yagiz, K., Foulad, D., Alzadeh, G. E., Tesarfreund, M., Muhammad, A.K.M. G., Puntel, M., Kroeger, K. M., Liu, C., Lee, S., Curtin, J. F., King, G. D., Lerner, J., Sato, K., Mineharu, Y., Xiong, W., Lowenstein, P. R., Castro, M. G.
(2009). Release of HMGB1 in Response to Proapoptotic Glioma Killing Strategies: Efficacy and Neurotoxicity. Clin. Cancer Res.
15: 4401-4414
[Abstract][Full Text]
McCabe, M. T., Brandes, J. C., Vertino, P. M.
(2009). Cancer DNA Methylation: Molecular Mechanisms and Clinical Implications. Clin. Cancer Res.
15: 3927-3937
[Abstract][Full Text]
Kitange, G. J., Carlson, B. L., Schroeder, M. A., Grogan, P. T., Lamont, J. D., Decker, P. A., Wu, W., James, C. D., Sarkaria, J. N.
(2009). Induction of MGMT expression is associated with temozolomide resistance in glioblastoma xenografts. Neuro Oncology
11: 281-291
[Abstract][Full Text]
Stupp, R., Roila, F., On behalf of the ESMO Guidelines Working Group,
(2009). Malignant glioma: ESMO Clinical Recommendations for diagnosis, treatment and follow-up. Ann Oncol
20: iv126-iv128
[Full Text]
McKean-Cowdin, R., Barnholtz-Sloan, J., Inskip, P. D., Ruder, A. M., Butler, M., Rajaraman, P., Razavi, P., Patoka, J., Wiencke, J. K., Bondy, M. L., Wrensch, M.
(2009). Associations between Polymorphisms in DNA Repair Genes and Glioblastoma. Cancer Epidemiol. Biomarkers Prev.
18: 1118-1126
[Abstract][Full Text]
Sauvageot, C. M.-E., Weatherbee, J. L., Kesari, S., Winters, S. E., Barnes, J., Dellagatta, J., Ramakrishna, N. R., Stiles, C. D., Kung, A. L.-J., Kieran, M. W., Wen, P. Y. C.
(2009). Efficacy of the HSP90 inhibitor 17-AAG in human glioma cell lines and tumorigenic glioma stem cells. Neuro Oncology
11: 109-121
[Abstract][Full Text]
Hoffmann, J., Fichtner, I., Lemm, M., Lienau, P., Hess-Stumpp, H., Rotgeri, A., Hofmann, B., Klar, U.
(2009). Sagopilone crosses the blood-brain barrier in vivo to inhibit brain tumor growth and metastases. Neuro Oncology
11: 158-166
[Abstract][Full Text]
Vaillant, B., Kuo, S.-H., de Groot, J.
(2009). Emerging Subspecialties in Neurology: Neuro-oncology: A developing subspecialty with many opportunities. Neurology
72: e51-e53
[Full Text]
Kadoch, C., Dinca, E. B., Voicu, R., Chen, L., Nguyen, D., Parikh, S., Karrim, J., Shuman, M. A., Lowell, C. A., Treseler, P. A., James, C. D., Rubenstein, J. L.
(2009). Pathologic Correlates of Primary Central Nervous System Lymphoma Defined in an Orthotopic Xenograft Model. Clin. Cancer Res.
15: 1989-1997
[Abstract][Full Text]
Glas, M., Happold, C., Rieger, J., Wiewrodt, D., Bahr, O., Steinbach, J. P., Wick, W., Kortmann, R.-D., Reifenberger, G., Weller, M., Herrlinger, U.
(2009). Long-Term Survival of Patients With Glioblastoma Treated With Radiotherapy and Lomustine Plus Temozolomide. JCO
27: 1257-1261
[Abstract][Full Text]
Brandes, A. A., Tosoni, A., Franceschi, E., Sotti, G., Frezza, G., Amista, P., Morandi, L., Spagnolli, F., Ermani, M.
(2009). Recurrence Pattern After Temozolomide Concomitant With and Adjuvant to Radiotherapy in Newly Diagnosed Patients With Glioblastoma: Correlation With MGMT Promoter Methylation Status. JCO
27: 1275-1279
[Abstract][Full Text]
Quinn, J. A., Jiang, S. X., Reardon, D. A., Desjardins, A., Vredenburgh, J. J., Rich, J. N., Gururangan, S., Friedman, A. H., Bigner, D. D., Sampson, J. H., McLendon, R. E., Herndon, J. E. II, Walker, A., Friedman, H. S.
(2009). Phase II Trial of Temozolomide Plus O6-Benzylguanine in Adults With Recurrent, Temozolomide-Resistant Malignant Glioma. JCO
27: 1262-1267
[Abstract][Full Text]
Chalmers, A. J.
(2009). The potential role and application of PARP inhibitors in cancer treatment. Br Med Bull
89: 23-40
[Abstract][Full Text]
OSHIRO, S., TSUGU, H., KOMATSU, F., OHMURA, T., OHTA, M., SAKAMOTO, S., FUKUSHIMA, T., INOUE, T.
(2009). Efficacy of Temozolomide Treatment in Patients with High-grade Glioma. Anticancer Res
29: 911-917
[Abstract][Full Text]
Blumenthal, D. T., Won, M., Mehta, M. P., Curran, W. J., Souhami, L., Michalski, J. M., Rogers, C. L., Corn, B. W.
(2009). Short Delay in Initiation of Radiotherapy May Not Affect Outcome of Patients With Glioblastoma: A Secondary Analysis From the Radiation Therapy Oncology Group Database. JCO
27: 733-739
[Abstract][Full Text]
Prados, M. D., Chang, S. M., Butowski, N., DeBoer, R., Parvataneni, R., Carliner, H., Kabuubi, P., Ayers-Ringler, J., Rabbitt, J., Page, M., Fedoroff, A., Sneed, P. K., Berger, M. S., McDermott, M. W., Parsa, A. T., Vandenberg, S., James, C. D., Lamborn, K. R., Stokoe, D., Haas-Kogan, D. A.
(2009). Phase II Study of Erlotinib Plus Temozolomide During and After Radiation Therapy in Patients With Newly Diagnosed Glioblastoma Multiforme or Gliosarcoma. JCO
27: 579-584
[Abstract][Full Text]
Remington, M., Chtchetinin, J., Ancheta, K., Nghiemphu, P. L., Cloughesy, T., Lai, A.
(2009). The L84F polymorphic variant of human O6-methylguanine-DNA methyltransferase alters stability in U87MG glioma cells but not temozolomide sensitivity. Neuro Oncology
11: 22-32
[Abstract][Full Text]
Wick, W., Platten, M., Weller, M.
(2009). New (alternative) temozolomide regimens for the treatment of glioma. Neuro Oncology
11: 69-79
[Abstract][Full Text]
Vredenburgh, J. J., Desjardins, A., Reardon, D. A., Friedman, H. S.
(2009). Experience with irinotecan for the treatment of malignant glioma. Neuro Oncology
11: 80-91
[Abstract][Full Text]
Miyashita, K., Kawakami, K., Nakada, M., Mai, W., Shakoori, A., Fujisawa, H., Hayashi, Y., Hamada, J.-i., Minamoto, T.
(2009). Potential Therapeutic Effect of Glycogen Synthase Kinase 3{beta} Inhibition against Human Glioblastoma. Clin. Cancer Res.
15: 887-897
[Abstract][Full Text]
Clarke, M. J., Mulligan, E. A., Grogan, P. T., Mladek, A. C., Carlson, B. L., Schroeder, M. A., Curtin, N. J., Lou, Z., Decker, P. A., Wu, W., Plummer, E. R., Sarkaria, J. N.
(2009). Effective sensitization of temozolomide by ABT-888 is lost with development of temozolomide resistance in glioblastoma xenograft lines. Molecular Cancer Therapeutics
8: 407-414
[Abstract][Full Text]
Bromberg, J. E. C., van den Bent, M. J.
(2009). Oligodendrogliomas: Molecular Biology and Treatment. The Oncologist
14: 155-163
[Abstract][Full Text]
Augustine, C. K., Yoo, J. S., Potti, A., Yoshimoto, Y., Zipfel, P. A., Friedman, H. S., Nevins, J. R., Ali-Osman, F., Tyler, D. S.
(2009). Genomic and Molecular Profiling Predicts Response to Temozolomide in Melanoma. Clin. Cancer Res.
15: 502-510
[Abstract][Full Text]
Moyes, V J, Alusi, G, Sabin, H I, Evanson, J, Berney, D M, Kovacs, K, Monson, J P, Plowman, P N, Drake, W M
(2009). Treatment of Nelson's syndrome with temozolomide. Eur J Endocrinol
160: 115-119
[Abstract][Full Text]
Schaich, M., Kestel, L., Pfirrmann, M., Robel, K., Illmer, T., Kramer, M., Dill, C., Ehninger, G., Schackert, G., Krex, D.
(2009). A MDR1 (ABCB1) gene single nucleotide polymorphism predicts outcome of temozolomide treatment in glioblastoma patients. Ann Oncol
20: 175-181
[Abstract][Full Text]
Sigmond, J., Honeywell, R. J., Postma, T. J., Dirven, C. M. F., de Lange, S. M., van der Born, K., Laan, A. C., Baayen, J. C. A., Van Groeningen, C. J., Bergman, A. M., Giaccone, G., Peters, G. J.
(2009). Gemcitabine uptake in glioblastoma multiforme: potential as a radiosensitizer. Ann Oncol
20: 182-187
[Abstract][Full Text]
Kesari, S., Schiff, D., Drappatz, J., LaFrankie, D., Doherty, L., Macklin, E. A., Muzikansky, A., Santagata, S., Ligon, K. L., Norden, A. D., Ciampa, A., Bradshaw, J., Levy, B., Radakovic, G., Ramakrishna, N., Black, P. M., Wen, P. Y.
(2009). Phase II Study of Protracted Daily Temozolomide for Low-Grade Gliomas in Adults. Clin. Cancer Res.
15: 330-337
[Abstract][Full Text]
Kulke, M. H., Hornick, J. L., Frauenhoffer, C., Hooshmand, S., Ryan, D. P., Enzinger, P. C., Meyerhardt, J. A., Clark, J. W., Stuart, K., Fuchs, C. S., Redston, M. S.
(2009). O6-Methylguanine DNA Methyltransferase Deficiency and Response to Temozolomide-Based Therapy in Patients with Neuroendocrine Tumors. Clin. Cancer Res.
15: 338-345
[Abstract][Full Text]
Pallini, R., Ricci-Vitiani, L., Banna, G. L., Signore, M., Lombardi, D., Todaro, M., Stassi, G., Martini, M., Maira, G., Larocca, L. M., De Maria, R.
(2008). Cancer Stem Cell Analysis and Clinical Outcome in Patients with Glioblastoma Multiforme. Clin. Cancer Res.
14: 8205-8212
[Abstract][Full Text]
Brown, P. D., Krishnan, S., Sarkaria, J. N., Wu, W., Jaeckle, K. A., Uhm, J. H., Geoffroy, F. J., Arusell, R., Kitange, G., Jenkins, R. B., Kugler, J. W., Morton, R. F., Rowland, K. M. Jr, Mischel, P., Yong, W. H., Scheithauer, B. W., Schiff, D., Giannini, C., Buckner, J. C.
(2008). Phase I/II Trial of Erlotinib and Temozolomide With Radiation Therapy in the Treatment of Newly Diagnosed Glioblastoma Multiforme: North Central Cancer Treatment Group Study N0177. JCO
26: 5603-5609
[Abstract][Full Text]
Wick, W., Stupp, R., Beule, A.-C., Bromberg, J., Wick, A., Ernemann, U., Platten, M., Marosi, C., Mason, W. P., van den Bent, M., Weller, M., Rorden, C., Karnath, H.-O., the European Organisation for Research and Treatme,
(2008). A novel tool to analyze MRI recurrence patterns in glioblastoma. Neuro Oncology
10: 1019-1024
[Abstract][Full Text]
Goldhoff, P., Warrington, N. M., Limbrick, D. D. Jr., Hope, A., Woerner, B. M., Jackson, E., Perry, A., Piwnica-Worms, D., Rubin, J. B.
(2008). Targeted Inhibition of Cyclic AMP Phosphodiesterase-4 Promotes Brain Tumor Regression. Clin. Cancer Res.
14: 7717-7725
[Abstract][Full Text]
Desjardins, A., Reardon, D. A., Herndon, J. E. II, Marcello, J., Quinn, J. A., Rich, J. N., Sathornsumetee, S., Gururangan, S., Sampson, J., Bailey, L., Bigner, D. D., Friedman, A. H., Friedman, H. S., Vredenburgh, J. J.
(2008). Bevacizumab Plus Irinotecan in Recurrent WHO Grade 3 Malignant Gliomas. Clin. Cancer Res.
14: 7068-7073
[Abstract][Full Text]
Duffy, M. J., Crown, J.
(2008). A Personalized Approach to Cancer Treatment: How Biomarkers Can Help. Clin. Chem.
54: 1770-1779
[Abstract][Full Text]
Bracht, L.-K., Wen, P., Meyerhardt, J. A., Kulke, M. H., Hornick, J. L., Redston, M., LaFrankie, D. C., Black, P. M., Kesari, S., Norden, A., Drappatz, J.
(2008). DNA Repair Enzyme Expression and Differential Response to Temozolomide in a Patient With Both Glioblastoma and Metastatic Pancreatic Neuroendocrine Tumor. JCO
26: 4843-4844
[Full Text]
Brait, M., Begum, S., Carvalho, A. L., Dasgupta, S., Vettore, A. L., Czerniak, B., Caballero, O. L., Westra, W. H., Sidransky, D., Hoque, M. O.
(2008). Aberrant Promoter Methylation of Multiple Genes during Pathogenesis of Bladder Cancer. Cancer Epidemiol. Biomarkers Prev.
17: 2786-2794
[Abstract][Full Text]
Gottardo, N. G., Gajjar, A.
(2008). Chemotherapy for Malignant Brain Tumors of Childhood. J Child Neurol
23: 1149-1159
[Abstract]
Fry, R. C., Svensson, J. P., Valiathan, C., Wang, E., Hogan, B. J., Bhattacharya, S., Bugni, J. M., Whittaker, C. A., Samson, L. D.
(2008). Genomic predictors of interindividual differences in response to DNA damaging agents. Genes Dev.
22: 2621-2626
[Abstract][Full Text]
Neyns, B., Cordera, S., Joosens, E., Nader, P.
(2008). Non-Hodgkin's Lymphoma in Patients With Glioma Treated With Temozolomide. JCO
26: 4518-4519
[Full Text]
Brandes, A. A., Franceschi, E., Tosoni, A.
(2008). In Reply. JCO
26: 4359-4360
[Full Text]
Hegi, M. E., Liu, L., Herman, J. G., Stupp, R., Wick, W., Weller, M., Mehta, M. P., Gilbert, M. R.
(2008). Correlation of O6-Methylguanine Methyltransferase (MGMT) Promoter Methylation With Clinical Outcomes in Glioblastoma and Clinical Strategies to Modulate MGMT Activity. JCO
26: 4189-4199
[Abstract][Full Text]
Linnebank, M., Semmler, A., Moskau, S., Smulders, Y., Blom, H., Simon, M.
(2008). The methylenetetrahydrofolate reductase (MTHFR) variant c.677C>T (A222V) influences overall survival of patients with glioblastoma multiforme. Neuro Oncology
10: 548-552
[Abstract][Full Text]
Wen, P. Y., Kesari, S.
(2008). Malignant Gliomas in Adults. NEJM
359: 492-507
[Full Text]
Mason, W. P., Cairncross, J. G.
(2008). Invited Article: The expanding impact of molecular biology on the diagnosis and treatment of gliomas. Neurology
71: 365-373
[Abstract][Full Text]
Beier, D., Rohrl, S., Pillai, D. R., Schwarz, S., Kunz-Schughart, L. A., Leukel, P., Proescholdt, M., Brawanski, A., Bogdahn, U., Trampe-Kieslich, A., Giebel, B., Wischhusen, J., Reifenberger, G., Hau, P., Beier, C. P.
(2008). Temozolomide Preferentially Depletes Cancer Stem Cells in Glioblastoma. Cancer Res.
68: 5706-5715
[Abstract][Full Text]
Hamstra, D. A., Galban, C. J., Meyer, C. R., Johnson, T. D., Sundgren, P. C., Tsien, C., Lawrence, T. S., Junck, L., Ross, D. J., Rehemtulla, A., Ross, B. D., Chenevert, T. L.
(2008). Functional Diffusion Map As an Early Imaging Biomarker for High-Grade Glioma: Correlation With Conventional Radiologic Response and Overall Survival. JCO
26: 3387-3394
[Abstract][Full Text]
Colman, H., Aldape, K.
(2008). Molecular Predictors in Glioblastoma: Toward Personalized Therapy. Arch Neurol
65: 877-883
[Abstract][Full Text]
Previous
