Dataset Information

GAPDH on EG-grid

ABSTRACT:

SUBMITTER: Junso Fujita

PROVIDER: EMPIAR-10955 | biostudies-other |

REPOSITORIES: biostudies-other

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Publications

Epoxidized graphene grid for highly efficient high-resolution cryoEM structural analysis.

Fujita Junso J Makino Fumiaki F Asahara Haruyasu H Moriguchi Maiko M Kumano Shota S Anzai Itsuki I Kishikawa Jun-Ichi JI Matsuura Yoshiharu Y Kato Takayuki T Namba Keiichi K Inoue Tsuyoshi T

Scientific reports 20230208 1

Functionalization of graphene is one of the most important fundamental technologies in a wide variety of fields including industry and biochemistry. We have successfully achieved a novel oxidative modification of graphene using photoactivated ClO2· as a mild oxidant and confirmed the oxidized graphene grid is storable with its functionality for at least three months under N2 atmosphere. Subsequent chemical functionalization enabled us to develop an epoxidized gra ...[more]

PMID: 36755111

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Project description:Glioblastoma (GBM) is the most common and lethal form of brain cancer (median survival <15 months). The DNA alkylating agent, temozolomide, is used as the standard chemotherapeutic agent, resulting in mispairing of guanine with thymidine that leads to cellular arrest. However, in GBM patients the O6-methylguanine-DNA methyltransferase (MGMT) protein protects DNA from damage induced by temozolomide. Nevertheless, loss of MGMT expression is a frequent event in human malignancies and typically the result of MGMT promoter methylation. MGMT methylation has been strongly associated with the T-allele of the rs16906252 SNP (C/T) in colorectal carcinoma, pleural mesothelioma, and lung cancers. We therefore examined the T-allele and MGMT methylation in temozolmide-treated GBM patients. In 255 temozolomide-treated GBM patients, we found that the T-allele was significantly more frequent in patients with a methylated MGMT promoter. The unadjusted hazard ratio for death in carriers of the T-allele compared to wild-type, irrespective of methylation status, was 0.39 (95%CI:0.21-0.73; p = 0.003), indicating a 61% relative reduction in the risk for death of T-allele carriers. Surprisingly, GBM patients harboring the T-allele in the absence of MGMT methylation showed a survival benefit comparable to those with MGMT methylation (median survival: 15.5 months) and significantly better than the median survival of wild-type, unmethylated patients (median survival: 10.3 months). This suggests that the T-allele may reduce MGMT activity by mechanisms independent of methylation. Genotyping of 451 healthy controls indicated the frequency of carriage of the T-allele was 13% (MAF 0.065). In contrast, carriage of the T-allele in 160 GBM patients was 17%. Significantly, elevated risks were associated with carriage of the T-allele and development of GBM (odds ratio of 2.62 [95%CI:1.7-4.2]). We report that the T-allele (rs16906252) has predictive (response to temozolomide) and prognostic value (MGMT methylation and longer survival), but conversely may be a predisposing factor for the development of GBM.

Dataset Information

GAPDH on EG-grid

Publications

Epoxidized graphene grid for highly efficient high-resolution cryoEM structural analysis.

Similar Datasets

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