Fractionated radiotherapy is the main stimulus for the induction of cell death and of Hsp70 release of p53 mutated glioblastoma cell lines

Radiation Oncology

Volumn 9, Issue 1, 2014, Pages

  Rubner, Yvonne ^a   Muth, Carolin ^a   Strnad, Annedore ^a   Derer, Anja ^a   Sieber, Renate ^a   Buslei, Rolf ^a   Frey, Benjamin ^a   Fietkau, Rainer ^a   Gaipl, Udo S ^a  

^a UNIVERSITY HOSPITAL ERLANGEN   (Germany)

Author keywords

Apoptosis; Clonogenic potential; Fractionated radiotherapy; G2 cell cycle arrest; Glioblastoma multiforme; Hsp70; Immunogenic cell death; Necrosis; Temozolomide; Valproic acid

Indexed keywords

HEAT SHOCK PROTEIN 70; HIGH MOBILITY GROUP B1 PROTEIN; PROTEIN P53; TEMOZOLOMIDE; VALPROIC ACID; ANTINEOPLASTIC AGENT; DACARBAZINE; HMGB1 PROTEIN, HUMAN; TP53 PROTEIN, HUMAN;

ARTICLE; CANCER CELL CULTURE; CANCER RADIOTHERAPY; CELL CYCLE; CELL DEATH; CLONOGENIC ASSAY; CONTROLLED STUDY; G2 PHASE CELL CYCLE CHECKPOINT; GENE MUTATION; GLIOBLASTOMA; HUMAN; HUMAN CELL; HUMAN CELL CULTURE; IN VITRO STUDY; RADIATION DOSE; STIMULUS; TUMOR MICROENVIRONMENT; WILD TYPE; ANALOGS AND DERIVATIVES; APOPTOSIS; BRAIN NEOPLASMS; CELL CYCLE G2 PHASE; CHEMISTRY; GENETICS; METABOLISM; MUTATION; NECROSIS; RADIATION DOSE FRACTIONATION; TUMOR CELL LINE;

ANTINEOPLASTIC AGENTS; APOPTOSIS; BRAIN NEOPLASMS; CELL CYCLE; CELL DEATH; CELL LINE, TUMOR; DACARBAZINE; DOSE FRACTIONATION; G2 PHASE; GLIOBLASTOMA; HMGB1 PROTEIN; HSP70 HEAT-SHOCK PROTEINS; HUMANS; MUTATION; NECROSIS; TUMOR SUPPRESSOR PROTEIN P53; VALPROIC ACID;

EID: 84899138473     PISSN: None     EISSN: 1748717X     Source Type: Journal    
DOI: 10.1186/1748-717X-9-89     Document Type: Article

References (86)

1. Bonavia R, Inda MM, Cavenee WK, Furnari FB. Heterogeneity maintenance in glioblastoma: a social network. Cancer Res 2011, 71:4055-4060. 10.1158/0008-5472.CAN-11-0153, 3117065, 21628493.
2. Stupp R, Hegi ME, Mason WP, van den Bent MJ, Taphoorn MJ, Janzer RC, Ludwin SK, Allgeier A, Fisher B, Belanger K, Hau P, Brandes AA, Gijtenbeek J, Marosi C, Vecht CJ, Mokhtari K, Wesseling P, Villa S, Eisenhauer E, Gorlia T, Weller M, Lacombe D, Cairncross JG, Mirimanoff RO European Organisation for Research and Treatment of Cancer Brain Tumour and Radiation Oncology Groups; National Cancer Institute of Canada Clinical Trials Group Effects of radiotherapy with concomitant and adjuvant temozolomide versus radiotherapy alone on survival in glioblastoma in a randomised phase III study: 5-year analysis of the EORTC-NCIC trial. Lancet Oncol 2009, 10:459-466. 10.1016/S1470-2045(09)70025-7, 19269895, European Organisation for Research and Treatment of Cancer Brain Tumour and Radiation Oncology Groups; National Cancer Institute of Canada Clinical Trials Group.
3. Kanzawa T, Germano IM, Komata T, Ito H, Kondo Y, Kondo S. Role of autophagy in temozolomide-induced cytotoxicity for malignant glioma cells. Cell Death Differ 2004, 11:448-457. 10.1038/sj.cdd.4401359, 14713959.
4. Brada M, Judson I, Beale P, Moore S, Reidenberg P, Statkevich P, Dugan M, Batra V, Cutler D. Phase I dose-escalation and pharmacokinetic study of temozolomide (SCH 52365) for refractory or relapsing malignancies. Br J Cancer 1999, 81:1022-1030. 10.1038/sj.bjc.6690802, 2362937, 10576660.
5. Denny BJ, Wheelhouse RT, Stevens MF, Tsang LL, Slack JA. NMR and molecular modeling investigation of the mechanism of activation of the antitumor drug temozolomide and its interaction with DNA. Biochemistry 1994, 33:9045-9051. 10.1021/bi00197a003, 8049205.
6. Silber JR, Bobola MS, Ghatan S, Blank A, Kolstoe DD, Berger MS. O6-methylguanine-DNA methyltransferase activity in adult gliomas: relation to patient and tumor characteristics. Cancer Res 1998, 58:1068-1073.
7. Blumenthal DT, Wade M, Rankin CJ, Fitzpatrick F, Stelzer K, Sloan A, Ackerley W, Rushing EJ. MGMT methylation in newly-diagnosed glioblastoma multiforme (GBM): From the S0001 phase III study of radiation therapy (RT) and 0(6)-benzylguanine, (0(6)BG) plus BCNU versus RT and BCNU alone for newly diagnosed GBM. J Clin Oncol 2006, 24:61S-61S.
8. Hirose Y, Berger MS, Pieper RO. p53 effects both the duration of G2/M arrest and the fate of temozolomide-treated human glioblastoma cells. Cancer Res 2001, 61:1957-1963.
9. Gunther W, Pawlak E, Damasceno R, Arnold H, Terzis AJ. Temozolomide induces apoptosis and senescence in glioma cells cultured as multicellular spheroids. Br J Cancer 2003, 88:463-469. 10.1038/sj.bjc.6600711, 2747547, 12569392.
10. Zhang WB, Wang Z, Shu F, Jin YH, Liu HY, Wang QJ, Yang Y. Activation of AMP-activated protein kinase by temozolomide contributes to apoptosis in glioblastoma cells via p53 activation and mTORC1 inhibition. J Biol Chem 2010, 285:40461-40471. 10.1074/jbc.M110.164046, 3003344, 20880848.
11. Kanzawa T, Bedwell J, Kondo Y, Kondo S, Germano IM. Inhibition of DNA repair for sensitizing resistant glioma cells to temozolomide. J Neurosurg 2003, 99:1047-1052. 10.3171/jns.2003.99.6.1047, 14705733.
12. van Breemen MS, Wilms EB, Vecht CJ. Epilepsy in patients with brain tumours: epidemiology, mechanisms, and management. Lancet Neurol 2007, 6:421-430. 10.1016/S1474-4422(07)70103-5, 17434097.
13. Weller M, Gorlia T, Cairncross JG, van den Bent MJ, Mason W, Belanger K, Brandes AA, Bogdahn U, Macdonald DR, Forsyth P, Rossetti AO, Lacombe D, Mirimanoff RO, Vecht CJ, Stupp R. Prolonged survival with valproic acid use in the EORTC/NCIC temozolomide trial for glioblastoma. Neurology 2011, 77:1156-1164. 10.1212/WNL.0b013e31822f02e1, 3265044, 21880994.
14. Perucca E. Pharmacological and therapeutic properties of valproate: a summary after 35 years of clinical experience. CNS Drugs 2002, 16:695-714. 10.2165/00023210-200216100-00004, 12269862.
15. Go HS, Seo JE, Kim KC, Han SM, Kim P, Kang YS, Han SH, Shin CY, Ko KH. Valproic acid inhibits neural progenitor cell death by activation of NF-kappaB signaling pathway and up-regulation of Bcl-XL. J Biomed Sci 2011, 18:48. 10.1186/1423-0127-18-48, 3158748, 21722408.
16. Phiel CJ, Zhang F, Huang EY, Guenther MG, Lazar MA, Klein PS. Histone deacetylase is a direct target of valproic acid, a potent anticonvulsant, mood stabilizer, and teratogen. J Biol Chem 2001, 276:36734-36741. 10.1074/jbc.M101287200, 11473107.
17. Li XN, Shu Q, Su JM, Perlaky L, Blaney SM, Lau CC. Valproic acid induces growth arrest, apoptosis, and senescence in medulloblastomas by increasing histone hyperacetylation and regulating expression of p21Cip1, CDK4, and CMYC. Mol Cancer Ther 2005, 4:1912-1922. 10.1158/1535-7163.MCT-05-0184, 16373706.
18. Fu J, Shao CJ, Chen FR, Ng HK, Chen ZP. Autophagy induced by valproic acid is associated with oxidative stress in glioma cell lines. Neuro Oncol 2010, 12:328-340. 10.1093/neuonc/nop005, 2940599, 20308311.
19. Van Nifterik KA, Van den Berg J, Slotman BJ, Lafleur MV, Sminia P, Stalpers LJ. Valproic acid sensitizes human glioma cells for temozolomide and gamma-radiation. J Neurooncol 2012, 107:61-67. 10.1007/s11060-011-0725-z, 22037799.
20. England B, Huang T, Karsy M. Current understanding of the role and targeting of tumor suppressor p53 in glioblastoma multiforme. Tumour Biol 2013, 34:2063-2074. 10.1007/s13277-013-0871-3, 23737287.
21. Giaccia AJ, Kastan MB. The complexity of p53 modulation: emerging patterns from divergent signals. Genes Dev 1998, 12:2973-2983. 10.1101/gad.12.19.2973, 9765199.
22. Anker L, Ohgaki H, Ludeke BI, Herrmann HD, Kleihues P, Westphal M. p53 protein accumulation and gene mutations in human glioma cell lines. Int J Cancer 1993, 55:982-987. 10.1002/ijc.2910550618, 8253536.
23. Quick QA, Gewirtz DA. An accelerated senescence response to radiation in wild-type p53 glioblastoma multiforme cells. J Neurosurg 2006, 105:111-118. 10.3171/jns.2006.105.1.111, 16871885.
24. Frey B, Rubner Y, Wunderlich R, Weiss EM, Pockley AG, Fietkau R, Gaipl US. Induction of abscopal anti-tumor immunity and immunogenic tumor cell death by ionizing irradiation - implications for cancer therapies. Curr Med Chem 2012, 19:1751-1764. 10.2174/092986712800099811, 22414083.
25. Frey B, Rubner Y, Kulzer L, Werthmoller N, Weiss EM, Fietkau R, Gaipl US. Antitumor immune responses induced by ionizing irradiation and further immune stimulation. Cancer Immunol Immunother 2014, 63:29-36. 10.1007/s00262-013-1474-y, 24052136.
26. Nowsheen S, Yang ES. The intersection between DNA damage response and cell death pathways. Exp Oncol 2012, 34:243-254. 3754840, 23070009.
27. Castedo M, Perfettini JL, Roumier T, Kroemer G. Cyclin-dependent kinase-1: linking apoptosis to cell cycle and mitotic catastrophe. Cell Death Differ 2002, 9:1287-1293. 10.1038/sj.cdd.4401130, 12478465.
28. Zitvogel L, Kepp O, Senovilla L, Menger L, Chaput N, Kroemer G. Immunogenic tumor cell death for optimal anticancer therapy: the calreticulin exposure pathway. Clin Cancer Res 2010, 16:3100-3104. 10.1158/1078-0432.CCR-09-2891, 20421432.
29. Tesniere A, Apetoh L, Ghiringhelli F, Joza N, Panaretakis T, Kepp O, Schlemmer F, Zitvogel L, Kroemer G. Immunogenic cancer cell death: a key-lock paradigm. Curr Opin Immunol 2008, 20:504-511. 10.1016/j.coi.2008.05.007, 18573340.
30. Garg AD, Nowis D, Golab J, Agostinis P. Photodynamic therapy: illuminating the road from cell death towards anti-tumour immunity. Apoptosis 2010, 15:1050-1071. 10.1007/s10495-010-0479-7, 20221698.
31. Kaczmarek A, Vandenabeele P, Krysko DV. Necroptosis: the release of damage-associated molecular patterns and its physiological relevance. Immunity 2013, 38:209-223. 10.1016/j.immuni.2013.02.003, 23438821.
32. Yuan J, Kroemer G. Alternative cell death mechanisms in development and beyond. Genes Dev 2010, 24:2592-2602. 10.1101/gad.1984410, 2994033, 21123646.
33. Duprez L, Takahashi N, Van Hauwermeiren F, Vandendriessche B, Goossens V, Vanden Berghe T, Declercq W, Libert C, Cauwels A, Vandenabeele P. RIP kinase-dependent necrosis drives lethal systemic inflammatory response syndrome. Immunity 2011, 35:908-918. 10.1016/j.immuni.2011.09.020, 22195746.
34. Gaipl US, Sheriff A, Franz S, Munoz LE, Voll RE, Kalden JR, Herrmann M. Inefficient clearance of dying cells and autoreactivity. Curr Top Microbiol Immunol 2006, 305:161-176.
35. Vanden Berghe T, Grootjans S, Goossens V, Dondelinger Y, Krysko DV, Takahashi N, Vandenabeele P. Determination of apoptotic and necrotic cell death in vitro and in vivo. Methods (San Diego, Calif) 2013, 61:117-129.
36. Golstein P, Kroemer G. Cell death by necrosis: towards a molecular definition. Trends Biochem Sci 2007, 32:37-43. 10.1016/j.tibs.2006.11.001, 17141506.
37. Chaurio RA, Janko C, Munoz LE, Frey B, Herrmann M, Gaipl US. Phospholipids: key players in apoptosis and immune regulation. Molecules (Basel, Switzerland) 2009, 14:4892-4914.
38. Banchereau J, Steinman RM. Dendritic cells and the control of immunity. Nature 1998, 392:245-252. 10.1038/32588, 9521319.
39. Pardoll DM, Topalian SL. The role of CD4+ T cell responses in antitumor immunity. Curr Opin Immunol 1998, 10:588-594. 10.1016/S0952-7915(98)80228-8, 9794842.
40. Rock KL, Gamble S, Rothstein L. Presentation of exogenous antigen with class I major histocompatibility complex molecules. Science 1990, 249:918-921. 10.1126/science.2392683, 2392683.
41. Tesei A, Sarnelli A, Arienti C, Menghi E, Medri L, Gabucci E, Pignatta S, Falconi M, Silvestrini R, Zoli W, D'Errico V, Romeo A, Parisi E, Polico R. In vitro irradiation system for radiobiological experiments. Radiat Oncol 2013, 8:257. 10.1186/1748-717X-8-257, 3874638, 24180359.
42. Mirzayans R, Andrais B, Scott A, Tessier A, Murray D. A sensitive assay for the evaluation of cytotoxicity and its pharmacologic modulation in human solid tumor-derived cell lines exposed to cancer-therapeutic agents. J Pharm Pharm Sci 2007, 10:298s-311s.
43. Galluzzi L, Aaronson SA, Abrams J, Alnemri ES, Andrews DW, Baehrecke EH, Bazan NG, Blagosklonny MV, Blomgren K, Borner C, Bredesen DE, Brenner C, Castedo M, Cidlowski JA, Ciechanover A, Cohen GM, De Laurenzi V, De Maria R, Deshmukh M, Dynlacht BD, El-Deiry WS, Flavell RA, Fulda S, Garrido C, Golstein P, Gougeon ML, Green DR, Gronemeyer H, Hajnóczky G, Hardwick JM, et al. Guidelines for the use and interpretation of assays for monitoring cell death in higher eukaryotes. Cell Death Differ 2009, 16:1093-1107. 10.1038/cdd.2009.44, 2757140, 19373242.
44. Riccardi C, Nicoletti I. Analysis of apoptosis by propidium iodide staining and flow cytometry. Nat Protoc 2006, 1:1458-1461. 10.1038/nprot.2006.238, 17406435.
45. Taghian A, DuBois W, Budach W, Baumann M, Freeman J, Suit H. In vivo radiation sensitivity of glioblastoma multiforme. Int J Radiat Oncol Biol Phys 1995, 32:99-104. 10.1016/0360-3016(94)00494-6, 7721644.
46. Williams JR, Zhang Y, Zhou H, Gridley DS, Koch CJ, Russell J, Slater JS, Little JB. A quantitative overview of radiosensitivity of human tumor cells across histological type and TP53 status. Int J Radiat Biol 2008, 84:253-264. 10.1080/09553000801953342, 18386191.
47. Williams JR, Zhang Y, Russell J, Koch C, Little JB. Human tumor cells segregate into radiosensitivity groups that associate with ATM and TP53 status. Acta Oncol 2007, 46:628-638. 10.1080/02841860601080407, 17562439.
48. Yao KC, Komata T, Kondo Y, Kanzawa T, Kondo S, Germano IM. Molecular response of human glioblastoma multiforme cells to ionizing radiation: cell cycle arrest, modulation of the expression of cyclin-dependent kinase inhibitors, and autophagy. J Neurosurg 2003, 98:378-384. 10.3171/jns.2003.98.2.0378, 12593626.
49. Lawrence YR, Vikram B, Dignam JJ, Chakravarti A, Machtay M, Freidlin B, Takebe N, Curran WJ, Bentzen SM, Okunieff P, Coleman CN, Dicker AP. NCI-RTOG translational program strategic guidelines for the early-stage development of radiosensitizers. J Natl Cancer Inst 2013, 105:11-24. 10.1093/jnci/djs472, 3536642, 23231975.
50. Rubner Y, Wunderlich R, Ruhle PF, Kulzer L, Werthmoller N, Frey B, Weiss EM, Keilholz L, Fietkau R, Gaipl US. How does ionizing irradiation contribute to the induction of anti-tumor immunity?. Front Oncol 2012, 2:75. 3404483, 22848871.
51. Ma Y, Kepp O, Ghiringhelli F, Apetoh L, Aymeric L, Locher C, Tesniere A, Martins I, Ly A, Haynes NM, Smyth MJ, Kroemer G, Zitvogel L. Chemotherapy and radiotherapy: cryptic anticancer vaccines. Semin Immunol 2010, 22:113-124. 10.1016/j.smim.2010.03.001, 20403709.
52. Jamal M, Rath BH, Williams ES, Camphausen K, Tofilon PJ. Microenvironmental regulation of glioblastoma radioresponse. Clin Cancer Res 2010, 16:6049-6059. 10.1158/1078-0432.CCR-10-2435, 3005074, 21037023.
53. Blough MD, Zlatescu MC, Cairncross JG. O6-methylguanine-DNA methyltransferase regulation by p53 in astrocytic cells. Cancer Res 2007, 67:580-584. 10.1158/0008-5472.CAN-06-2782, 17234766.
54. Kitange GJ, Carlson BL, Schroeder MA, Grogan PT, Lamont JD, Decker PA, Wu W, James CD, Sarkaria JN. Induction of MGMT expression is associated with temozolomide resistance in glioblastoma xenografts. Neuro Oncol 2009, 11:281-291. 10.1215/15228517-2008-090, 2718972, 18952979.
55. Yip S, Miao J, Cahill DP, Iafrate AJ, Aldape K, Nutt CL, Louis DN. MSH6 mutations arise in glioblastomas during temozolomide therapy and mediate temozolomide resistance. Clin Cancer Res 2009, 15:4622-4629. 10.1158/1078-0432.CCR-08-3012, 2737355, 19584161.
56. Barker CA, Bishop AJ, Chang M, Beal K, Chan TA. Valproic acid use during radiation therapy for glioblastoma associated with improved survival. Int J Radiat Oncol Biol Phys 2013, 86:504-509. 10.1016/j.ijrobp.2013.02.012, 23523186.
57. Ardon H, Van Gool S, Lopes IS, Maes W, Sciot R, Wilms G, Demaerel P, Bijttebier P, Claes L, Goffin J, Van Calenbergh F, De Vleeschouwer S. Integration of autologous dendritic cell-based immunotherapy in the primary treatment for patients with newly diagnosed glioblastoma multiforme: a pilot study. J Neurooncol 2010, 99:261-272. 10.1007/s11060-010-0131-y, 20146084.
58. Matsui Y, Tsuchida Y, Keng PC. Effects of p53 mutations on cellular sensitivity to ionizing radiation. Am J Clin Oncol 2001, 24:486-490. 10.1097/00000421-200110000-00014, 11586101.
59. Stupp R, Mason WP, van den Bent MJ, Weller M, Fisher B, Taphoorn MJ, Belanger K, Brandes AA, Marosi C, Bogdahn U, Curschmann J, Janzer RC, Ludwin SK, Gorlia T, Allgeier A, Lacombe D, Cairncross JG, Eisenhauer E, Mirimanoff RO European Organisation for Research and Treatment of Cancer Brain Tumor and Radiotherapy Groups; National Cancer Institute of Canada Clinical Trials Group Radiotherapy plus concomitant and adjuvant temozolomide for glioblastoma. N Engl J Med 2005, 352:987-996. 10.1056/NEJMoa043330, 15758009, European Organisation for Research and Treatment of Cancer Brain Tumor and Radiotherapy Groups; National Cancer Institute of Canada Clinical Trials Group.
60. Yoshino A, Ogino A, Yachi K, Ohta T, Fukushima T, Watanabe T, Katayama Y, Okamoto Y, Naruse N, Sano E, Tsumoto K. Gene expression profiling predicts response to temozolomide in malignant gliomas. Int J Oncol 2010, 36:1367-1377.
61. Ryu CH, Yoon WS, Park KY, Kim SM, Lim JY, Woo JS, Jeong CH, Hou Y, Jeun SS. Valproic acid downregulates the expression of MGMT and sensitizes temozolomide-resistant glioma cells. J Biomed Biotechnol 2012, 2012:987495. 3373250, 22701311.
62. Beier D, Rohrl S, Pillai DR, Schwarz S, Kunz-Schughart LA, Leukel P, Proescholdt M, Brawanski A, Bogdahn U, Trampe-Kieslich A, Giebel B, Wischhusen J, Reifenberger G, Hau P, Beier CP. Temozolomide preferentially depletes cancer stem cells in glioblastoma. Cancer Res 2008, 68:5706-5715. 10.1158/0008-5472.CAN-07-6878, 18632623.
63. Hermisson M, Klumpp A, Wick W, Wischhusen J, Nagel G, Roos W, Kaina B, Weller M. O6-methylguanine DNA methyltransferase and p53 status predict temozolomide sensitivity in human malignant glioma cells. J Neurochem 2006, 96:766-776. 10.1111/j.1471-4159.2005.03583.x, 16405512.
64. Fietkau R, Putz F, Lahmer G, Semrau S, Buslei R. Can MGMT promoter methylation status be used as a prognostic and predictive marker for glioblastoma multiforme at the present time? A word of caution. Strahlenther Onkol 2013, 189:993-995. 10.1007/s00066-013-0459-2, 24177536.
65. Chen X, Wong P, Radany E, Wong JY. HDAC inhibitor, valproic acid, induces p53-dependent radiosensitization of colon cancer cells. Cancer Biother Radiopharm 2009, 24:689-699. 10.1089/cbr.2009.0629, 2920759, 20025549.
66. Das PM, Singal R. DNA methylation and cancer. J Clin Oncol 2004, 22:4632-4642. 10.1200/JCO.2004.07.151, 15542813.
67. Lauber K, Ernst A, Orth M, Herrmann M, Belka C. Dying cell clearance and its impact on the outcome of tumor radiotherapy. Front Oncol 2012, 2:116. 3438527, 22973558.
68. Orth M, Lauber K, Niyazi M, Friedl AA, Li M, Maihofer C, Schuttrumpf L, Ernst A, Niemoller OM, Belka C. Current concepts in clinical radiation oncology. Radiat Environ Biophys 2014, 53(1):1-29. 10.1007/s00411-013-0497-2, 3935099, 24141602.
69. Roos WP, Batista LF, Naumann SC, Wick W, Weller M, Menck CF, Kaina B. Apoptosis in malignant glioma cells triggered by the temozolomide-induced DNA lesion O6-methylguanine. Oncogene 2007, 26:186-197. 10.1038/sj.onc.1209785, 16819506.
70. Jakubowicz-Gil J, Langner E, Badziul D, Wertel I, Rzeski W. Apoptosis induction in human glioblastoma multiforme T98G cells upon temozolomide and quercetin treatment. Tumour Biol 2013, 34:2367-2378. 10.1007/s13277-013-0785-0, 3713258, 23580181.
71. Milanovic D, Firat E, Grosu AL, Niedermann G. Increased radiosensitivity and radiothermosensitivity of human pancreatic MIA PaCa-2 and U251 glioblastoma cell lines treated with the novel Hsp90 inhibitor NVP-HSP990. Radiat Oncol 2013, 8:42. 10.1186/1748-717X-8-42, 3599905, 23448094.
72. Weiss EM, Wunderlich R, Ebel N, Rubner Y, Schlucker E, Meyer-Pittroff R, Ott OJ, Fietkau R, Gaipl US, Frey B. Selected anti-tumor vaccines merit a place in multimodal tumor therapies. Front Oncol 2012, 2:132. 3466463, 23087898.
73. Nakada M, Furuta T, Hayashi Y, Minamoto T, Hamada J. The strategy for enhancing temozolomide against malignant glioma. Front Oncol 2012, 2:98. 3418701, 22912934.
74. Chinnaiyan P, Cerna D, Burgan WE, Beam K, Williams ES, Camphausen K, Tofilon PJ. Postradiation sensitization of the histone deacetylase inhibitor valproic acid. Clin Cancer Res 2008, 14:5410-5415. 10.1158/1078-0432.CCR-08-0643, 3393085, 18765532.
75. Chen CH, Chang YJ, Ku MS, Chung KT, Yang JT. Enhancement of temozolomide-induced apoptosis by valproic acid in human glioma cell lines through redox regulation. J Mol Med (Berl) 2011, 89:303-315. 10.1007/s00109-010-0707-1, 21340685.
76. Multhoff G, Pockley AG, Streffer C, Gaipl US. Dual role of heat shock proteins (HSPs) in anti-tumor immunity. Curr Mol Med 2012, 12:1174-1182. 10.2174/156652412803306666, 22804240.
77. Schmid TE, Multhoff G. Radiation-induced stress proteins - the role of heat shock proteins (HSP) in anti- tumor responses. Curr Med Chem 2012, 19:1765-1770. 10.2174/092986712800099767, 22414085.
78. Gehrmann M, Marienhagen J, Eichholtz-Wirth H, Fritz E, Ellwart J, Jaattela M, Zilch T, Multhoff G. Dual function of membrane-bound heat shock protein 70 (Hsp70), Bag-4, and Hsp40: protection against radiation-induced effects and target structure for natural killer cells. Cell Death Differ 2005, 12:38-51. 10.1038/sj.cdd.4401510, 15592361.
79. Schildkopf P, Frey B, Mantel F, Ott OJ, Weiss EM, Sieber R, Janko C, Sauer R, Fietkau R, Gaipl US. Application of hyperthermia in addition to ionizing irradiation fosters necrotic cell death and HMGB1 release of colorectal tumor cells. Biochem Biophys Res Commun 2010, 391:1014-1020. 10.1016/j.bbrc.2009.12.008, 19968962.
80. Schildkopf P, Frey B, Ott OJ, Rubner Y, Multhoff G, Sauer R, Fietkau R, Gaipl US. Radiation combined with hyperthermia induces HSP70-dependent maturation of dendritic cells and release of pro-inflammatory cytokines by dendritic cells and macrophages. Radiother Oncol 2011, 101:109-115. 10.1016/j.radonc.2011.05.056, 21704416.
81. Rodel F, Frey B, Multhoff G, Gaipl U. Contribution of the immune system to bystander and non-targeted effects of ionizing radiation. Cancer Lett 2013, doi:10.1016/j.canlet.2013.09.015.
82. Fadul CE, Fisher JL, Hampton TH, Lallana EC, Li Z, Gui J, Szczepiorkowski ZM, Tosteson TD, Rhodes CH, Wishart HA, Lewis LD, Ernstoff MS. Immune response in patients with newly diagnosed glioblastoma multiforme treated with intranodal autologous tumor lysate-dendritic cell vaccination after radiation chemotherapy. J Immunother (Hagerstown, Md: 1997) 2011, 34:382-389.
83. Jie X, Hua L, Jiang W, Feng F, Feng G, Hua Z. Clinical application of a dendritic cell vaccine raised against heat-shocked glioblastoma. Cell Biochem Biophys 2012, 62:91-99. 10.1007/s12013-011-9265-6, 21909820.
84. Wheeler CJ, Black KL, Liu G, Mazer M, Zhang XX, Pepkowitz S, Goldfinger D, Ng H, Irvin D, Yu JS. Vaccination elicits correlated immune and clinical responses in glioblastoma multiforme patients. Cancer Res 2008, 68:5955-5964. 10.1158/0008-5472.CAN-07-5973, 18632651.
85. Yamanaka R, Abe T, Yajima N, Tsuchiya N, Homma J, Kobayashi T, Narita M, Takahashi M, Tanaka R. Vaccination of recurrent glioma patients with tumour lysate-pulsed dendritic cells elicits immune responses: results of a clinical phase I/II trial. Br J Cancer 2003, 89:1172-1179. 10.1038/sj.bjc.6601268, 2394324, 14520441.
86. Ardon H, Van Gool SW, Verschuere T, Maes W, Fieuws S, Sciot R, Wilms G, Demaerel P, Goffin J, Van Calenbergh F, Menten J, Clement P, Debiec-Rychter M, De Vleeschouwer S. Integration of autologous dendritic cell-based immunotherapy in the standard of care treatment for patients with newly diagnosed glioblastoma: results of the HGG-2006 phase I/II trial. Cancer Immunol Immunother 2012, 61:2033-2044. 10.1007/s00262-012-1261-1, 22527250.