PubMed · 7773057
The source did not provide an abstract. Follow the original record for more information.
Explore connections, maps & timelines
A G Dalgleish. 1995-05-20. Chemotherapy for solid tumours.. https://doi.org/10.1136/bmj.310.6990.1328c
Cite the original work for its findings. Save a collection to share your selection of sources.
KEEP EXPLORING
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.
Much attention has recently focused on the observation that UV light can activate the long terminal repeat (LTR) of the human immunodeficiency virus (HIV). Although the mechanism of LTR activation remains obscure, several lines of investigation have suggested that it is a result of activation of the NF-kappa B transcription factor(s) following signaling events related to generalized DNA damage. In this report, we present data demonstrating that HIV LTR activation is not a general consequence of cellular DNA damage, but rather a process unique to specific genotoxic stimuli, and that it does not necessarily depend on activation of NF-kappa B. Furthermore, we demonstrate that several of these agents can significantly increase HIV replication and accelerate CD4-positive lymphocyte cytotoxicity in vitro. These findings, therefore, could have clinical significance to AIDS patients with malignancies who are undergoing radiotherapy and chemotherapy.
Explore the source record for details and available documents.