Intranasal perillyl alcohol therapy improves survival of patients with recurrent glioblastoma harboring mutant variant for MTHFR rs1801133 polymorphism

Faria, Giselle Marianne; Soares, Igor D. P.; Salazar, Marcela d’Alincourt; Amorim, Márcia Rodrigues; Pessôa, Bruno Lima; Fonseca, Clóvis Orlando da; Quirico-Santos, Thereza

doi:10.1186/s12885-020-06802-8

Cited by 12 publications

(8 citation statements)

References 49 publications

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“…Reduced enzymatic activity has also been associated with the MGMT promoter and DNA hypomethylation [ 124 ]. Additionally, a retrospective cohort of patients with recurrent GBM presented genomic DNA hypomethylation [ 125 ]. The authors demonstrated that the MTHFR 677TT genotype was associated with reduced DNA methylation and suggested that patients harboring the MTHFR 677TT could benefit from treatment with a new approach based on perillyl alcohol inhalation.…”

Section: Mthfr C677t and A1298c Polymorphisms And Gliomamentioning

confidence: 99%

MTHFR C677T and A1298C Polymorphisms in Breast Cancer, Gliomas and Gastric Cancer: A Review

Petrone

Bernardo

Santos

et al. 2021

Genes

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Folate (vitamin B9) is found in some water-soluble foods or as a synthetic form of folic acid and is involved in many essential biochemical processes. Dietary folate is converted into tetrahydrofolate, a vital methyl donor for most methylation reactions, including DNA methylation. 5,10-methylene tetrahydrofolate reductase (MTHFR) is a critical enzyme in the folate metabolism pathway that converts 5,10-methylenetetrahydrofolate into 5-methyltetrahydrofolate, which produces a methyl donor for the remethylation of homocysteine to methionine. MTHFR polymorphisms result in reduced enzyme activity and altered levels of DNA methylation and synthesis. MTHFR polymorphisms have been linked to increased risks of several pathologies, including cancer. Breast cancer, gliomas and gastric cancer are highly heterogeneous and aggressive diseases associated with high mortality rates. The impact of MTHFR polymorphisms on these tumors remains controversial in the literature. This review discusses the relationship between the MTHFR C677T and A1298C polymorphisms and the increased risk of breast cancer, gliomas, and gastric cancer. Additionally, we highlight the relevance of ethnic and dietary aspects of population-based studies and histological stratification of highly heterogeneous tumors. Finally, this review discusses these aspects as potential factors responsible for the controversial literature concerning MTHFR polymorphisms.

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Section: Mthfr C677t and A1298c Polymorphisms And Gliomamentioning

confidence: 99%

MTHFR C677T and A1298C Polymorphisms in Breast Cancer, Gliomas and Gastric Cancer: A Review

Petrone

Bernardo

Santos

et al. 2021

Genes

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“…Due to their minimal cytotoxicity 13 , 14 , EOs are considered pharmaceutically safe and could represent a good alternative natural source of anticancer agents, thus deserving further investigations to ascertain their mechanism of action and to validate their possible clinical uses as alternative/complementary antitumor agents. In the last 20 years, preclinical studies demonstrated anticancer activity of either some EOs or their main components 15 , 16 and led to case–control studies 17 and clinical trials 18 – 20 . At present, EOs are used to ameliorate cancer patients’ quality of life and clinical trials are ongoing to evaluate their efficacy or the efficacy of their components in cancer patients (NCT02336087, NCT03449303, NCT04560114, NCT04449315, NCT00003219, NCT00003238, NCT01459172, NCT01046929, NCT04296266).…”

Section: Introductionmentioning

confidence: 99%

Antitumor effect of Melaleuca alternifolia essential oil and its main component terpinen-4-ol in combination with target therapy in melanoma models

et al. 2021

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Essential oils (EOs) have been recently emerging for their promising biological activities in preventing tumorigenesis or progression of different tumor histotypes, including melanoma. In this study, we investigated the antitumor activity of a panel of EOs in different tumor models. The ability of Melaleuca alternifolia (tea tree oil) and its main component, terpinen-4-ol, to sensitize the target therapy currently used for melanoma treatment was also assessed. Our results demonstrated that EOs differently affect the viability of human cancer cells and led us to select six EOs effective in melanoma and lung cancer cells, without toxic effects in human fibroblasts. When combined with dabrafenib and/or trametinib, Melaleuca alternifolia synergistically reduced the viability of melanoma cells by activating apoptosis. Through machine learning classification modeling, α-terpineol, tepinolene, and terpinen-4-ol, three components of Melaleuca alternifolia, were identified as the most likely relevant components responsible for the EO’s antitumor effect. Among them, terpinen-4-ol was recognized as the Melaleuca alternifolia component responsible for its antitumor and proapoptotic activity. Overall, our study holds promise for further analysis of EOs as new anticancer agents and supports the rationale for their use to improve target therapy response in melanoma.

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“…Studies have shown that the 5-year survival rate is only approximately 5% (Stupp et al, 2009;Ostrom et al, 2017). Due to the high cost of treatment of glioblastoma and poor treatment effect, it has always been one of the difficulties in tumor treatment (Cloughesy et al, 2020;Faria et al, 2020;Reardon et al, 2020). Therefore, it is of great importance to find effective molecular targets and improve the prognosis of glioblastoma.…”

Section: Introductionmentioning

confidence: 99%

SUMOylation Regulator-Related Molecules Can Be Used as Prognostic Biomarkers for Glioblastoma

Meng

2021

Front. Cell Dev. Biol.

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IntroductionSUMOylation is one of the post-translational modifications. The relationship between the expression of SUMOylation regulators and the prognosis of glioblastoma is not quite clear.Materials and MethodsThe single nucleotide variant data, the transcriptome data, and survival information were acquired from The Cancer Genome Atlas, Gene Expression Omnibus, and cBioportal database. Wilcoxon test was used to analyze differentially expressed genes between glioblastoma and normal brain tissues. Gene set enrichment analysis was conducted to find the possible functions. One risk scoring model was built by the least absolute shrinkage and selection operator Cox regression. Kaplain–Meier survival curves and receiver operating characteristic curves were applied to evaluate the effectiveness of the model in predicting the prognosis of glioblastoma.ResultsSingle-nucleotide variant mutations were found in SENP7, SENP3, SENP5, PIAS3, RANBP2, USPL1, SENP1, PIAS2, SENP2, and PIAS1. Moreover, UBE2I, UBA2, PIAS3, and SENP1 were highly expressed in glioblastoma, whereas PIAS1, RANBP2, SENP5, and SENP2 were downregulated in glioblastoma. Functional enrichment analysis showed that the SUMOylation regulators of glioblastoma might involve cell cycle, DNA replication, and other functions. A prognostic model of glioblastoma was constructed based on SUMOylation regulator-related molecules (ATF7IP, CCNB1IP1, and LBH). Kaplain–Meier survival curves and receiver operating characteristic curves showed that the model had a strong ability to predict the overall survival of glioblastoma.ConclusionThis study analyzed the expression of 15 SUMOylation regulators in glioblastoma. The risk assessment model was constructed based on the SUMOylation regulator-related genes, which had a strong predictive ability for the overall survival of patients with glioblastoma. It might provide targets for the study of the relationship between SUMOylation and glioblastoma.

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Intranasal perillyl alcohol therapy improves survival of patients with recurrent glioblastoma harboring mutant variant for MTHFR rs1801133 polymorphism

Cited by 12 publications

References 49 publications

MTHFR C677T and A1298C Polymorphisms in Breast Cancer, Gliomas and Gastric Cancer: A Review

MTHFR C677T and A1298C Polymorphisms in Breast Cancer, Gliomas and Gastric Cancer: A Review

Antitumor effect of Melaleuca alternifolia essential oil and its main component terpinen-4-ol in combination with target therapy in melanoma models

SUMOylation Regulator-Related Molecules Can Be Used as Prognostic Biomarkers for Glioblastoma

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