Additive Effects of 5-Aza-2’-deoxycytidine and Irradiation on Clonogenic Survival of Human Medulloblastoma Cell Lines

Patties, Ina; Jahns, J; Hildebrandt, Guido; Kortmann, Rolf‐Dieter; Glasow, Annegret

doi:10.1007/s00066-009-1956-1

Cited by 21 publications

(31 citation statements)

References 38 publications

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“…For examples, decitabine (5-Aza) has been reported to enhance radiosensitivity through activating G2/M checkpoint responses, inducing apoptosis in osteosarcoma [61], breast cancer [62], colorectal cancer [63], medulloblastoma [64], and head-and-neck cancers [30-31]. Our results may provide an explanation for the phenomenon that inhibitors of DNMT or EZH2 reverse repressive epigenomes to resensitize radioresistant cancer cells to ionizing radiation.…”

Section: Discussionmentioning

confidence: 68%

DNA methylome analysis identifies epigenetic silencing of FHIT as a determining factor for radiosensitivity in oral cancer: an outcome-predicting and treatment-implicating study

et al. 2014

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Radioresistance is still an emerging problem for radiotherapy of oral cancer. Aberrant epigenetic alterations play an important role in cancer development, yet the role of such alterations in radioresistance of oral cancer is not fully explored. Using a methylation microarray, we identified promoter hypermethylation of FHIT (fragile histidine triad) in radioresistant OML1-R cells, established from hypo-fractionated irradiation of parental OML1 radiosensitive oral cancer cells. Further analysis confirmed that transcriptional repression of FHIT was due to promoter hypermethylation, H3K27me3 and overexpression of methyltransferase EZH2 in OML1-R cells. Epigenetic interventions or depletion of EZH2 restored FHIT expression. Ectopic expression of FHIT inhibited tumor growth in both in vitro and in vivo models, while also resensitizing radioresistant cancer cells to irradiation, by restoring Chk2 phosphorylation and G2/M arrest. Clinically, promoter hypermethylation of FHIT inversely correlated with its expression and independently predicted both locoregional control and overall survival in 40 match-paired oral cancer patient samples. Further in vivo therapeutic experiments confirmed that inhibition of DNA methylation significantly resensitized radioresistant oral cancer cell xenograft tumors. These results show that epigenetic silencing of FHIT contributes partially to radioresistance and predicts clinical outcomes in irradiated oral cancer. The radiosensitizing effect of epigenetic interventions warrants further clinical investigation.

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Section: Discussionmentioning

confidence: 68%

DNA methylome analysis identifies epigenetic silencing of FHIT as a determining factor for radiosensitivity in oral cancer: an outcome-predicting and treatment-implicating study

et al. 2014

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“…Therefore, new strategies to enhance ther- [5,15,22,23,24,29]. We previously reported on the ability of the histone deacetylase inhibitor SAHA to radiosensitize human tumor cell lines [3].…”

Section: Discussionmentioning

confidence: 99%

Suberoylanilide hydroxamic acid affects γH2AX expression in osteosarcoma, atypical teratoid rhabdoid tumor and normal tissue cell lines after irradiation

et al. 2012

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SAHA increases radiosensitivity in tumor but not normal tissue cell lines. The increased H2AX phosphorylation status of the SAHA-treated tumor cells post irradiation likely reflects its delayed dephosphorylation within the DNA damage signal decay rather than chromatin acetylation-dependent differences in the overall efficacy of DSB induction and rejoining. The results support the hypothesis that combining SAHA with irradiation may provide a promising strategy in the treatment of solid tumors.

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“…Newly developed techniques could minimize problems of matching fields and maximize precision of craniospinal radiotherapy in future [9]. Moreover the potential clinical application of new chemotherapeutic agents merits further investigation [23].…”

Section: Discussionmentioning

confidence: 99%

Curative treatment for central nervous system medulloepithelioma despite residual disease after resection

et al. 2011

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Medulloepithelioma of the central nervous system (CNS) is an uncommon primitive neuroectodermal tumor (PNET) usually occurring in early childhood. It is characterized by highly malignant behavior with a propensity for progression, recurrence, and dissemination despite intensive therapy. Due to its rarity, the optimal management is still unknown. However, gross total resection (GTR) has been considered crucial to achieve cure. In this article, the authors report on 2 cases of CNS medulloepithelioma in which long-term survival (more than 6 years) could be achieved despite evidence of, or suspected postoperative residual disease with an otherwise dismal prognosis.The patients were treated according to different strata of the protocol for primitive neuroectodermal tumors (PNET) of the German-Austrian multicenter trial of the German Society for Pediatric Oncology and Hematology (GPOH) for childhood brain tumors (HIT 2000). Treatment included postoperative hyperfractionated radiotherapy of the craniospinal axis followed by a boost to the tumor site in combination with chemotherapy. A review of the 2 reported and 37 previously published cases confirmed GTR and older age as positive prognostic factors.

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Additive Effects of 5-Aza-2’-deoxycytidine and Irradiation on Clonogenic Survival of Human Medulloblastoma Cell Lines

Abstract: 5-aza-dC did not enhance radiation sensitivity of MB cells but significantly reduced the clonogenicity versus irradiation alone, which merits further investigation of its potential clinical application in MB possibly by combination with other chemotherapeutic agents.

Cited by 21 publications

References 38 publications

DNA methylome analysis identifies epigenetic silencing of FHIT as a determining factor for radiosensitivity in oral cancer: an outcome-predicting and treatment-implicating study

DNA methylome analysis identifies epigenetic silencing of FHIT as a determining factor for radiosensitivity in oral cancer: an outcome-predicting and treatment-implicating study

Suberoylanilide hydroxamic acid affects γH2AX expression in osteosarcoma, atypical teratoid rhabdoid tumor and normal tissue cell lines after irradiation

Curative treatment for central nervous system medulloepithelioma despite residual disease after resection

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