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Microbiome analyses of blood and tissues suggest cancer diagnostic approach 期刊论文
NATURE, 2020, 579 (7800) : 567-+
作者:  Shao, Zhengping;  Flynn, Ryan A.;  Crowe, Jennifer L.;  Zhu, Yimeng;  Liang, Jialiang;  Jiang, Wenxia;  Aryan, Fardin;  Aoude, Patrick;  Bertozzi, Carolyn R.;  Estes, Verna M.;  Lee, Brian J.;  Bhagat, Govind;  Zha, Shan;  Calo, Eliezer
收藏  |  浏览/下载:87/0  |  提交时间:2020/07/03

Microbial nucleic acids are detected in samples of tissues and blood from more than 10,000 patients with cancer, and machine learning is used to show that these can be used to discriminate between and among different types of cancer, suggesting a new microbiome-based diagnostic approach.


Systematic characterization of the cancer microbiome provides the opportunity to develop techniques that exploit non-human, microorganism-derived molecules in the diagnosis of a major human disease. Following recent demonstrations that some types of cancer show substantial microbial contributions(1-10), we re-examined whole-genome and whole-transcriptome sequencing studies in The Cancer Genome Atlas(11) (TCGA) of 33 types of cancer from treatment-naive patients (a total of 18,116 samples) for microbial reads, and found unique microbial signatures in tissue and blood within and between most major types of cancer. These TCGA blood signatures remained predictive when applied to patients with stage Ia-IIc cancer and cancers lacking any genomic alterations currently measured on two commercial-grade cell-free tumour DNA platforms, despite the use of very stringent decontamination analyses that discarded up to 92.3% of total sequence data. In addition, we could discriminate among samples from healthy, cancer-free individuals (n = 69) and those from patients with multiple types of cancer (prostate, lung, and melanoma  100 samples in total) solely using plasma-derived, cell-free microbial nucleic acids. This potential microbiome-based oncology diagnostic tool warrants further exploration.


  
Robust and persistent reactivation of SIV and HIV by N-803 and depletion of CD8(+) cells 期刊论文
NATURE, 2020, 578 (7793) : 154-+
作者:  Diaz-Cuadros, Margarete;  Wagner, Daniel E.;  Budjan, Christoph;  Hubaud, Alexis;  Tarazona, Oscar A.;  Donelly, Sophia;  Michaut, Arthur;  Al Tanoury, Ziad;  Yoshioka-Kobayashi, Kumiko;  Niino, Yusuke;  Kageyama, Ryoichiro;  Miyawaki, Atsushi;  Touboul, Jonathan;  Pourquie, Olivier
收藏  |  浏览/下载:45/0  |  提交时间:2020/07/03

Human immunodeficiency virus (HIV) persists indefinitely in individuals with HIV who receive antiretroviral therapy (ART) owing to a reservoir of latently infected cells that contain replication-competent virus(1-4). Here, to better understand the mechanisms responsible for latency persistence and reversal, we used the interleukin-15 superagonist N-803 in conjunction with the depletion of CD8(+) lymphocytes in ART-treated macaques infected with simian immunodeficiency virus (SIV). Although N-803 alone did not reactivate virus production, its administration after the depletion of CD8(+) lymphocytes in conjunction with ART treatment induced robust and persistent reactivation of the virus in vivo. We found viraemia of more than 60 copies per ml in all macaques (n = 14  100%) and in 41 out of a total of 56 samples (73.2%) that were collected each week after N-803 administration. Notably, concordant results were obtained in ART-treated HIV-infected humanized mice. In addition, we observed that co-culture with CD8(+) T cells blocked the in vitro latency-reversing effect of N-803 on primary human CD4(+) T cells that were latently infected with HIV. These results advance our understanding of the mechanisms responsible for latency reversal and lentivirus reactivation during ART-suppressed infection.


The interleukin-15 superagonist N-803, combined with the depletion of CD8(+) lymphocytes, induced a robust and persistent reactivation of the virus in vivo in both antiretroviral-therapy-treated SIV-infected macaques and HIV-infected humanized mice.


  
100-N Area Decision Unit Target Analyte List Development for Soil 科技报告
来源:US Department of Energy (DOE). 出版年: 2012
作者:  Ovink, R.
收藏  |  浏览/下载:14/0  |  提交时间:2019/04/05
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