PubMed · 8639391
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L W Kwak, D L Longo. 1996. Lymphomas.. https://pubmed.ncbi.nlm.nih.gov/8639391/
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Drug response differs substantially in cancer patients due to inter- and intra-tumor heterogeneity. Particularly, transcriptome context, especially tumor microenvironment, has been shown playing a significant role in shaping the actual treatment outcome. In this study, we develop a deep variational autoencoder (VAE) model to compress thousands of genes into latent vectors in a low-dimensional space. We then demonstrate that these encoded vectors could accurately impute drug response, outperform standard signature-gene based approaches, and appropriately control the overfitting problem. We apply rigorous quality assessment and validation, including assessing the impact of cell line lineage, cross-validation, cross-panel evaluation, and application in independent clinical data sets, to warrant the accuracy of the imputed drug response in both cell lines and cancer samples. Specifically, the expression-regulated component (EReX) of the observed drug response achieves high correlation across panels. Using the well-trained models, we impute drug response of The Cancer Genome Atlas data and investigate the features and signatures associated with the imputed drug response, including cell line origins, somatic mutations and tumor mutation burdens, tumor microenvironment, and confounding factors. In summary, our deep learning method and the results are useful for the study of signatures and markers of drug response.
Animal and in vitro studies provide evidence of an anticarcinogenic potential of active ingredients in teas. This review encompasses epidemiologic studies of stomach, colon, and lung cancer as well as the evidence of a relationship between tea drinking and cancer at large in humans. Cohort studies do not suggest a protective role for tea drinking in the total risk of cancer. Site-specific studies reveal a more complex picture. The epidemiologic studies on tea drinking and stomach cancer do not justify claims of a cancer-protective effect. A protective effect of green tea on the development of colon cancer is suggested. The evidence regarding black tea is less clear, with some indication of a risk of colon or rectal cancer associated with regular use of black tea. The studies on tea and lung cancer also suggest an increased risk with increased tea consumption. The range and crude categorization of tea consumption, choice of control groups, and inadequate control for confounding might have obscured possible relationships. From the limited studies that suggest a favorable effect from tea, it is likely that benefits are restricted to high intakes in high-risk populations.
Flaxseed and its major mammalian lignan precursor secoisolariciresinol diglycoside have been shown to be protective against chemically induced carcinogenesis in animal models. Although flaxseed is the richest source of mammalian lignan precursors, it is not known whether these levels vary with source. Thus the objective of this study was to determine how lignan levels in flaxseed are affected by variety, growing location, harvest year, and seeding time. Ten varieties of flaxseed (AC Linora, Andro, Flanders, Linott, McGregor, Noralta, NorLin, NorMan, Somme, and Vimy) were subjected to 1) in vitro fermentation with human fecal inoculum for 24 hours under anaerobic conditions to assess mammalian lignan production and 2) high-performance liquid chromatography (HPLC) analysis for secoisolariciresinol levels. Three of these varieties (Linott, McGregor, and NorLin) were grown in four locations, seeded early (May) for three different years, and, in one year, seeded early (May) or late (June). Significant differences in lignan production were observed among the different varieties, ranging from 0.96 mumol/g for Linott to 3.15 mumol/g for Somme flaxseed (p < 0.05). Growing location had significant effects on lignan production from all three varieties. Harvest year significantly affected only the Linott variety (p < 0.05), whereas seeding time had no effect. A significant correlation (r = 0.572, p < 0.003) was observed between lignan values obtained from HPLC and in vitro fermentation methods, indicating that HPLC analysis of flaxseed may be used as a predictor of its lignan production levels. Differences due to variety, harvest location, and harvest year of flaxseed should be taken into consideration when tumorigenesis studies are designed.