Enhanced radiosensitivity of malignant glioma cells after adenoviral p53 transduction

Broaddus, William C.; Liu, Yue; Steele, Laura L.; Gillies, G. T.; Lin, Peck‐Sun; Loudon, William G.; Valerie, Kristoffer; Schmidt‐Ullrich, Rupert; Fillmore, Helen

doi:10.3171/jns.1999.91.6.0997

Cited by 69 publications

(27 citation statements)

References 17 publications

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“…1 Tumor cells carrying p53 mutations are resistant to apoptosis induced by DNA damage, while an overexpression of wild-type p53 enhances the radiosensitivity of glioma cells. [33][34][35] However, the effect of p53 mutations on the efficacy of radio-and chemosensitivity in patients with gliomas, especially GBMs, remains controversial. Some have reported that the p53 status of GBM patients did not affect their survival 22,29 or p53 Mutations in Glioma/Shiraishi et al p53 Mutations in Glioma/Shiraishi et al…”

Section: Discussionmentioning

confidence: 99%

Influence of p53 mutations on prognosis of patients with glioblastoma

Shiraishi¹,

Tada²,

Nakamura³

et al. 2002

Cancer

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BACKGROUNDThe influence of p53 mutations on the biology of astrocytic tumors is controversial. p53 is thought to be inactivated in the early stage of gliomagenesis; however, what role its inactivation plays in the malignancy of gliomas remains unknown. To understand the significance of p53 inactivation, the authors identified the locus of p53 gene mutation in glioma samples at different stages of progression and studied the correlation between the mutation and clinical behavior.METHODSSamples from newly diagnosed gliomas, including pure and mixed astrocytomas, were analyzed for p53 mutations using a yeast functional assay. To determine the locus of the gene mutations, DNA sequencing was performed.RESULTSThe incidence of p53 mutations was higher in anaplastic astrocytomas (AA, 48%) than glioblastomas (GBM, 31%). There was no significant difference in the average ages of GBM patients with and without p53 mutations (54.9 years ± 2.3 and 53.2 years ± 4.6, respectively). In GBM patients, the mutation did not affect progression free survival or overall survival. Astrocytomas and GBM differed in the distribution of p53 mutation loci.CONCLUSIONSThe p53 gene mutation does not markedly affect the survival of GBM patients. The difference in the location of p53 mutations between AA and GBM suggests that in gliomas, the p53 mutation may contribute not only to tumorigenesis (as an early event) but also to progression to malignancy (as a late event). Cancer 2002;95:249–57. © 2002 American Cancer Society.DOI 10.1002/cncr.10677

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Section: Discussionmentioning

confidence: 99%

Influence of p53 mutations on prognosis of patients with glioblastoma

Shiraishi¹,

Tada²,

Nakamura³

et al. 2002

Cancer

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“…Hence, the multimodality approach including radiation therapy is a common strategy for gliomas. Some reports have shown the advantage of additional radiation therapy to gene therapy, such as p53 gene 12,13 and ganciclovir (GCV ) /herpes simplex virus thymidine kinase ( HSV-TK ) prodrug /enzyme therapies. 14 -18 Additionally, combined therapy with 5-FC /CD treatment plus radiation was reported to have a therapeutic advantage compared to 5-FC /CD therapy alone.…”

Section: Discussionmentioning

confidence: 99%

“…12,17 Histological analysis of longitudinally surviving rats was not documented. Consequently, we were unable to compare brain alterations to the Kim and Broaddus data.…”

Section: Discussionmentioning

confidence: 99%

Combined radiation and gene therapy for brain tumors with adenovirus-mediated transfer of cytosine deaminase and uracil phosphoribosyltransferase genes

et al. 2002

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“…[2][3][4][5] The molecular basis of GBM resistance has not been fully elucidated. However, overexpression or amplification of epidermal growth factor receptor (EGFR), 6 PTEN and p53 mutations 7,8 and expression of PKC-Z 9 have been postulated to contribute to the lack of efficacy of chemotherapy and radiation in the treatment of GBMs and other cancers. Activation of EGFR stimulates a number of signal transduction pathways, including the Ras/Raf/mitogen-activated protein kinase (MAPK), Ras/PI3K/Akt/mTOR and PKC signaling pathways.…”

Section: Introductionmentioning

confidence: 99%

Farnesylthiosalicylic acid induces caspase activation and apoptosis in glioblastoma cells

et al. 2005

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Primary glioblastomas (GBMs) commonly overexpress the oncogene epidermal growth factor receptor (EGFR), which leads to increased Ras activity. FTA, a novel Ras inhibitor, produced both time-and dose-dependent caspase-mediated apoptosis in GBM cell lines. EGFR-mediated increase in 3 Hthymidine uptake was inhibited by FTA. FACS analysis was performed to determine the percent of apoptotic cells. The sub-Go population of GBM cells was increased from 4.5 to 13.8% (control) to over 45-53.6% in FTA-treated cells within 24 h. Furthermore, FTA also increased the activities of both caspase-3 and -9, and PARP cleavage. Treatment of GBMs with FTA before or after EGF addition to the cultures blocked phosphorylation of Akt and mitogen-activated protein kinases (MAPK). FTA also significantly reduced the amount of EGFinduced Ras-GTP as reflected by a decrease in the level of Ras bound to Raf-RBD-GST. This study demonstrates that inhibition of Ras methylation may provide a therapeutic target for the treatment of GBMs overexpressing EGFR.

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Enhanced radiosensitivity of malignant glioma cells after adenoviral p53 transduction

Cited by 69 publications

References 17 publications

Influence of p53 mutations on prognosis of patients with glioblastoma

Influence of p53 mutations on prognosis of patients with glioblastoma

Combined radiation and gene therapy for brain tumors with adenovirus-mediated transfer of cytosine deaminase and uracil phosphoribosyltransferase genes

Farnesylthiosalicylic acid induces caspase activation and apoptosis in glioblastoma cells

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