• 文献检索
  • 文档翻译
  • 深度研究
  • 学术资讯
  • Suppr Zotero 插件Zotero 插件
  • 邀请有礼
  • 套餐&价格
  • 历史记录
应用&插件
Suppr Zotero 插件Zotero 插件浏览器插件Mac 客户端Windows 客户端微信小程序
定价
高级版会员购买积分包购买API积分包
服务
文献检索文档翻译深度研究API 文档MCP 服务
关于我们
关于 Suppr公司介绍联系我们用户协议隐私条款
关注我们

Suppr 超能文献

核心技术专利：CN118964589B侵权必究
粤ICP备2023148730 号-1Suppr @ 2026

文献检索

告别复杂PubMed语法，用中文像聊天一样搜索，搜遍4000万医学文献。AI智能推荐，让科研检索更轻松。

立即免费搜索

文件翻译

保留排版，准确专业，支持PDF/Word/PPT等文件格式，支持 12+语言互译。

免费翻译文档

深度研究

AI帮你快速写综述，25分钟生成高质量综述，智能提取关键信息，辅助科研写作。

立即免费体验

能量代谢在放疗抵抗性直肠癌中发生改变。

Energy Metabolism Is Altered in Radioresistant Rectal Cancer.

机构信息

Department of Surgery, School of Medicine, Trinity Translational Medicine Institute, Trinity St James's Cancer Institute, Trinity College Dublin, D08 NHY1 Dublin, Ireland.

UCD School of Agriculture and Food Science, UCD Institute of Food and Health, Conway Institute, University College Dublin, D04 V1W8 Dublin, Ireland.

出版信息

Int J Mol Sci. 2023 Apr 11;24(8):7082. doi: 10.3390/ijms24087082.

DOI:10.3390/ijms24087082
PMID:37108244
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC10138551/
Abstract

Resistance to neoadjuvant chemoradiation therapy is a significant clinical challenge in the management of rectal cancer. There is an unmet need to identify the underlying mechanisms of treatment resistance to enable the development of biomarkers predictive of response and novel treatment strategies to improve therapeutic response. In this study, an in vitro model of inherently radioresistant rectal cancer was identified and characterized to identify mechanisms underlying radioresistance in rectal cancer. Transcriptomic and functional analysis demonstrated significant alterations in multiple molecular pathways, including the cell cycle, DNA repair efficiency and upregulation of oxidative phosphorylation-related genes in radioresistant SW837 rectal cancer cells. Real-time metabolic profiling demonstrated decreased reliance on glycolysis and enhanced mitochondrial spare respiratory capacity in radioresistant SW837 cells when compared to radiosensitive HCT116 cells. Metabolomic profiling of pre-treatment serum samples from rectal cancer patients ( = 52) identified 16 metabolites significantly associated with subsequent pathological response to neoadjuvant chemoradiation therapy. Thirteen of these metabolites were also significantly associated with overall survival. This study demonstrates, for the first time, a role for metabolic reprograming in the radioresistance of rectal cancer in vitro and highlights a potential role for altered metabolites as novel circulating predictive markers of treatment response in rectal cancer patients.

摘要

新辅助放化疗耐药是直肠癌治疗的重大临床挑战。目前迫切需要明确治疗耐药的潜在机制，以便开发预测反应的生物标志物和改善治疗反应的新治疗策略。本研究鉴定并表征了一种固有放射抵抗的直肠癌体外模型，以确定直肠癌放射抵抗的潜在机制。转录组学和功能分析表明，多个分子途径发生了显著改变，包括放射抵抗的 SW837 直肠癌细胞中的细胞周期、DNA 修复效率和氧化磷酸化相关基因的上调。与放射敏感的 HCT116 细胞相比，实时代谢组学分析显示放射抵抗的 SW837 细胞对糖酵解的依赖性降低，线粒体备用呼吸能力增强。对 52 例直肠癌患者新辅助放化疗前的血清样本进行代谢组学分析，鉴定出 16 种与新辅助放化疗后病理反应显著相关的代谢物。其中 13 种代谢物与总生存期也显著相关。本研究首次证明代谢重编程在直肠癌体外放射抵抗中的作用，并强调了改变的代谢物作为直肠癌患者治疗反应的新型循环预测标志物的潜在作用。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a5ae/10138551/610c8e873ca2/ijms-24-07082-g007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a5ae/10138551/79e1e9f98d74/ijms-24-07082-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a5ae/10138551/19f72fd610da/ijms-24-07082-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a5ae/10138551/b871fc6ec40a/ijms-24-07082-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a5ae/10138551/6b5ff0659c39/ijms-24-07082-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a5ae/10138551/cb6551dc0e37/ijms-24-07082-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a5ae/10138551/9ad2edd6375c/ijms-24-07082-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a5ae/10138551/610c8e873ca2/ijms-24-07082-g007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a5ae/10138551/79e1e9f98d74/ijms-24-07082-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a5ae/10138551/19f72fd610da/ijms-24-07082-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a5ae/10138551/b871fc6ec40a/ijms-24-07082-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a5ae/10138551/6b5ff0659c39/ijms-24-07082-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a5ae/10138551/cb6551dc0e37/ijms-24-07082-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a5ae/10138551/9ad2edd6375c/ijms-24-07082-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a5ae/10138551/610c8e873ca2/ijms-24-07082-g007.jpg

相似文献

1
Energy Metabolism Is Altered in Radioresistant Rectal Cancer.能量代谢在放疗抵抗性直肠癌中发生改变。
Int J Mol Sci. 2023 Apr 11;24(8):7082. doi: 10.3390/ijms24087082.
2
CoA Synthase () Mediates Radiation Resistance via PI3K Signaling in Rectal Cancer.辅酶 A 合成酶 () 通过 PI3K 信号通路介导直肠癌的辐射抵抗。
Cancer Res. 2020 Jan 15;80(2):334-346. doi: 10.1158/0008-5472.CAN-19-1161. Epub 2019 Nov 8.
3
Prediction of Poor Response to Neoadjuvant Chemoradiation in Patients With Rectal Cancer Using a DNA Repair Deregulation Score: Picking the Losers Instead of the Winners.利用 DNA 修复失调评分预测直肠癌患者对新辅助放化疗的不良反应：挑出失败者，而不是胜利者。
Dis Colon Rectum. 2020 Mar;63(3):300-309. doi: 10.1097/DCR.0000000000001564.
4
Predictive Significance of Mucinous Histology on Pathologic Complete Response Rate Following Capecitabine-Based Neoadjuvant Chemoradiation in Rectal Cancer: a Comparative Study.黏液组织学对直肠癌中基于卡培他滨的新辅助放化疗后病理完全缓解率的预测意义：一项对比研究
J Gastrointest Cancer. 2019 Dec;50(4):716-722. doi: 10.1007/s12029-018-0136-x.
5
Complement is increased in treatment resistant rectal cancer and modulates radioresistance.补充剂在治疗抵抗性直肠癌中增加，并调节放射抵抗性。
Cancer Lett. 2024 Nov 1;604:217253. doi: 10.1016/j.canlet.2024.217253. Epub 2024 Sep 14.
6
Metformin is a metabolic modulator and radiosensitiser in rectal cancer.二甲双胍是一种直肠癌中的代谢调节剂和放射增敏剂。
Front Oncol. 2023 Aug 3;13:1216911. doi: 10.3389/fonc.2023.1216911. eCollection 2023.
7
Altered mitochondrial function and energy metabolism is associated with a radioresistant phenotype in oesophageal adenocarcinoma.线粒体功能和能量代谢的改变与食管腺癌的放射抗性表型相关。
PLoS One. 2014 Jun 26;9(6):e100738. doi: 10.1371/journal.pone.0100738. eCollection 2014.
8
A novel high-risk model identified by epithelial-mesenchymal transition predicts prognosis and radioresistance in rectal cancer.一种新型上皮-间充质转化高风险模型预测直肠癌的预后和放射抵抗性。
Mol Carcinog. 2024 Nov;63(11):2119-2132. doi: 10.1002/mc.23797. Epub 2024 Jul 26.
9
Gene expression profile is associated with chemoradiation resistance in rectal cancer.基因表达谱与直肠癌的放化疗抵抗有关。
Colorectal Dis. 2014 Jan;16(1):57-66. doi: 10.1111/codi.12395.
10
MicroRNA expression profile associated with response to neoadjuvant chemoradiotherapy in locally advanced rectal cancer patients.与局部晚期直肠癌患者新辅助放化疗反应相关的 microRNA 表达谱。
Radiat Oncol. 2012 Nov 20;7:195. doi: 10.1186/1748-717X-7-195.

引用本文的文献

1
Novel radiation and targeted therapy combinations for improving rectal cancer outcomes.新型放疗与靶向治疗联合方案改善直肠癌预后
Expert Rev Mol Med. 2024 Apr 16;26:e14. doi: 10.1017/erm.2024.15.
2
Albumin-based nanosystem for dual-modality imaging-guided chem-phototherapy against immune-cold triple-negative breast cancer.用于双模态成像引导化学光热疗法治疗免疫冷三阴性乳腺癌的白蛋白基纳米系统
Regen Biomater. 2023 Aug 31;10:rbad073. doi: 10.1093/rb/rbad073. eCollection 2023.
3
Metformin is a metabolic modulator and radiosensitiser in rectal cancer.

本文引用的文献

1
Phosphatidylcholine-Derived Lipid Mediators: The Crosstalk Between Cancer Cells and Immune Cells.磷脂酰胆碱衍生的脂质介质：癌细胞与免疫细胞的串扰。
Front Immunol. 2022 Feb 15;13:768606. doi: 10.3389/fimmu.2022.768606. eCollection 2022.
2
Hypoxia in Solid Tumors: How Low Oxygenation Impacts the "Six Rs" of Radiotherapy.实体瘤中的缺氧：低氧环境如何影响放疗的“六 R”。
Front Endocrinol (Lausanne). 2021 Sep 2;12:742215. doi: 10.3389/fendo.2021.742215. eCollection 2021.
3
Metabolomics in cancer research and emerging applications in clinical oncology.
二甲双胍是一种直肠癌中的代谢调节剂和放射增敏剂。
Front Oncol. 2023 Aug 3;13:1216911. doi: 10.3389/fonc.2023.1216911. eCollection 2023.
癌症研究中的代谢组学及其在临床肿瘤学中的新兴应用。
CA Cancer J Clin. 2021 Jul;71(4):333-358. doi: 10.3322/caac.21670. Epub 2021 May 13.
4
Global Cancer Statistics 2020: GLOBOCAN Estimates of Incidence and Mortality Worldwide for 36 Cancers in 185 Countries.《全球癌症统计数据 2020：全球 185 个国家和地区 36 种癌症的发病率和死亡率估计》。
CA Cancer J Clin. 2021 May;71(3):209-249. doi: 10.3322/caac.21660. Epub 2021 Feb 4.
5
NOTCH Activation via gp130/STAT3 Signaling Confers Resistance to Chemoradiotherapy.通过gp130/STAT3信号通路激活NOTCH赋予对放化疗的抗性。
Cancers (Basel). 2021 Jan 26;13(3):455. doi: 10.3390/cancers13030455.
6
JmjC-KDMs KDM3A and KDM6B modulate radioresistance under hypoxic conditions in esophageal squamous cell carcinoma.JmjC-KDMs KDM3A 和 KDM6B 在低氧条件下调节食管鳞癌细胞的放射抵抗性。
Cell Death Dis. 2020 Dec 14;11(12):1068. doi: 10.1038/s41419-020-03279-y.
7
Impact of hypoxia on the double-strand break repair after photon and carbon ion irradiation of radioresistant HNSCC cells.缺氧对耐辐射头颈部鳞癌细胞光子和碳离子照射后双链断裂修复的影响。
Sci Rep. 2020 Dec 7;10(1):21357. doi: 10.1038/s41598-020-78354-7.
8
Recent advances in (chemo-)radiation therapy for rectal cancer: a comprehensive review.直肠癌放化疗的最新进展：综合述评。
Radiat Oncol. 2020 Nov 10;15(1):262. doi: 10.1186/s13014-020-01695-0.
9
Targeting cancer-cell mitochondria and metabolism to improve radiotherapy response.靶向癌细胞线粒体与代谢以改善放疗反应。
Transl Oncol. 2021 Jan;14(1):100905. doi: 10.1016/j.tranon.2020.100905. Epub 2020 Oct 14.
10
Real-time metabolic profiling of oesophageal tumours reveals an altered metabolic phenotype to different oxygen tensions and to treatment with Pyrazinib.实时代谢组学分析食管肿瘤显示，不同氧张力和吡唑尼布治疗会导致代谢表型改变。
Sci Rep. 2020 Jul 21;10(1):12105. doi: 10.1038/s41598-020-68777-7.