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Effects of the Green Tea Polyphenol Epigallocatechin-3-Gallate on Glioma: A Critical Evaluation of the Literature.

Effects of the Green Tea Polyphenol Epigallocatechin-3-Gallate on Glioma: A Critical Evaluation of the Literature.

Nutr Cancer. 2018 Mar 23;:1-17

Authors: Le CT, Leenders WPJ, Molenaar RJ, van Noorden CJF

Abstract The review discusses the effects of Epigallocatechin-3-gallate Gallate (EGCG) on glioma as a basis for future research on clinical application of EGCG. Epidemiological studies on the effects of green tea or EGCG on the risk of glioma is inconclusive due to the limited number of studies, the inclusion of all tea types in these studies, and the focus on caffeine rather than EGCG. In vivo experiments using EGCG monotherapy are inconclusive. Nevertheless, EGCG induces cell death, prevents cellular proliferation, and limits invasion in multiple glioma cell lines. Furthermore, EGCG enhances the efficacy of anti-glioma therapies, including irradiation, temozolomide, carmustine, cisplatin, tamoxifen, and TNF-related apoptosis-inducing ligand, but reduces the effect of bortezomib. Pro-drugs, co-treatment, and encapsulation are being investigated to enhance clinical applicability of EGCG. Mechanisms of actions of EGCG have been partly elucidated. EGCG has both anti-oxidant and oxidant properties. EGCG inhibits pro-survival proteins, such as telomerase, survivin, GRP78, PEA15, and P-gp. EGCG inhibits signaling of PDGFR, IGF-1R, and 67LR. EGCG reduces invasiveness of cancer cells by inhibiting the activities of various metalloproteinases, cytokines, and chemokines. Last, EGCG inhibits some NADPH-producing enzymes, thus disturbing redox status and metabolism of glioma cells. In conclusion, EGCG may be a suitable adjuvant to potentiate anti-glioma therapies.

PMID: 29570984 [PubMed - as supplied by publisher]

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Proteomic Features of Colorectal Cancer Identify Tumor Subtypes Independent of Oncogenic Mutations and Independently Predict Relapse-Free Survival

Abstract

Background

The directed study of the functional proteome in colorectal cancer (CRC) has identified critical protein markers and signaling pathways; however, the prognostic relevance of many of these proteins remains unclear.

Methods

We determined the prognostic implications of the functional proteome in 263 CRC tumor samples from patients treated at MD Anderson Cancer Center (MDACC) and 462 patients from The Cancer Genome Atlas (TCGA) to identify patterns of protein expression that drive tumorigenesis. A total of 163 validated proteins were analyzed by reverse phase protein array (RPPA). Unsupervised hierarchical clustering of the tumor proteins from the MDACC cohort was performed, and clustering was validated using RPPA data from TCGA CRC. Cox regression was used to identify predictors of tumor recurrence.

Results

Clustering revealed dichotomization, with subtype A notable for a high epithelial-mesenchymal transition (EMT) protein signature, while subtype B was notable for high Akt/TSC/mTOR pathway components. Survival data were only available for the MDACC cohort and were used to evaluate prognostic relevance of these protein signatures. Group B demonstrated worse relapse-free survival (hazard ratio 2.11, 95% confidence interval 1.04–4.27, p = 0.039), although there was no difference in known genomic drivers between the two proteomic groups. Proteomic grouping and stage were significant predictors of recurrence on multivariate analysis. Eight proteins were found to be significant predictors of tumor recurrence on multivariate analysis: Collagen VI, FOXO3a, INPP4B, LcK, phospho-PEA15, phospho-PRAS40, Rad51, phospho-S6.

Conclusion

CRC can be classified into distinct subtypes by proteomic features independent of common oncogenic driver mutations. Proteomic analysis has identified key biomarkers with prognostic importance, however these findings require further validation in an independent cohort.

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