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用于转移性结直肠癌特征分析的分子工具

Molecular Tools for Metastatic Colorectal Cancer Characterization.

作者信息

Maitra Radhashree, Fogel Elisha, Parakrama Ruwan, Goel Sanjay

机构信息

Montefiore Medical Center, 1695 Eastchester Road Bronx, New York 10461, USA.

Albert Einstein College of Medicine, 1300 Morris Park Ave, Bronx, NY 10461, USA.

出版信息

J Cell Immunol. 2020;2(6):359-363. doi: 10.33696/immunology.2.067.

Abstract

In our recent publication [1], we have explored at the molecular level the consequences of reovirus administration to patients with mutated colorectal cancer (CRC). This was the first reported study where transcriptome assay was performed on mutated CRC patients receiving reovirus (pelareorep) therapy. Using peripheral mononuclear cells as a tumor surrogate, we have identified several hundred genes that were significantly altered in a transcriptome assay of patients receiving pelareorep serving as their own controls (pre and post reovirus administration) and compared to untreated controls [2]. We focused primarily on 884 immune related genes and published the data for genes with significance probability of 0.001 (1 in thousand for a perfect random occurrence). Samples were collected at 48 hours, day 8 and day 15 post reovirus administration and compared for dynamic gene expression alterations over time. Using PBMC we also performed flow cytometry, cytokine ELISA, immunohistochemistry, and determination of the expression level of CRC specific microRNA miR-29a-3p. Our data supports the therapeutic competence of reovirus and identifies the four major ways by which it exerts its antitumor effects.

摘要

在我们最近的出版物[1]中,我们在分子水平上探究了将呼肠孤病毒给予患有突变型结直肠癌(CRC)患者的后果。这是首次报道的对接受呼肠孤病毒(pelareorep)治疗的突变型CRC患者进行转录组分析的研究。使用外周血单核细胞作为肿瘤替代物,我们在接受pelareorep治疗的患者的转录组分析中鉴定了数百个显著改变的基因,这些患者以自身作为对照(呼肠孤病毒给药前后)并与未治疗的对照进行比较[2]。我们主要关注884个免疫相关基因,并公布了显著性概率为0.001(千分之一的完全随机发生概率)的基因数据。在呼肠孤病毒给药后48小时、第8天和第15天收集样本,并比较随时间的动态基因表达变化。使用外周血单核细胞,我们还进行了流式细胞术、细胞因子酶联免疫吸附测定、免疫组织化学以及CRC特异性微小RNA miR-29a-3p表达水平的测定。我们的数据支持呼肠孤病毒的治疗能力,并确定了其发挥抗肿瘤作用的四种主要方式。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b9a5/7793569/695d546a4158/nihms-1645479-f0001.jpg

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